Pharmacological properties of the drug Eglonil
Neuroleptic drug. Sulpiride is a selective antagonist of dopamine D2/D3 receptors. In patients with psychosis with negative symptoms, sulpiride is effective at a dose of 150–600 mg/day; at this dose, sulpiride has virtually no effect on positive symptoms. At a dose of 0.6–1.6 g/day, it improves the condition of patients with acute or chronic psychosis with positive symptoms. Only very high doses of sulpiride have a sedative effect. After intramuscular administration at a dose of 100 mg, the maximum concentration of the drug in the blood plasma (about 2.2 mg/l) is achieved after 30 minutes. When taken orally, sulpiride is absorbed in the digestive tract within 4.5 hours, the maximum concentration of the drug in the blood plasma ranges from 0.5–1.8 mg/l after taking a dose of 200 mg. Bioavailability of oral forms is 25–35% with wide individual variations; the concentration of sulpiride in blood plasma is proportional to the dose. Sulpiride is rapidly distributed in body tissues, mainly in the kidneys and liver; a small amount penetrates the BBB. Less than 40% of the drug binds to plasma proteins; the distribution ratio of erythrocytes and blood plasma is 1. The amount of the drug that passes into breast milk is 1/1000 part of the daily dose. Sulpiride is poorly metabolized in the body. The half-life is 7 hours; volume of distribution at steady state is 0.94 l/kg (0.6–1.5 l/kg) body weight. Total clearance - 126 ml/min. Sulpiride is excreted mainly by the kidneys by glomerular filtration.
The Many Faces of Eglonil
B
For more than 20 years,
Eglonil
(generic name -
sulpiride
) has been widely used not only in psychiatry, but also in other areas of medicine due to its diverse clinical effects.
Eglonil belongs to the group of atypical antipsychotics
, and therefore, in the early years of clinical study, most studies were aimed at determining its effectiveness in psychotic disorders. However, the accumulation of clinical data has revealed a wide range of effectiveness of Eglonil, as well as its important differences from classical antipsychotics. This is largely due to the pharmacological properties of Eglonil and its special effect on dopamine receptors (O'Connor SE, Brown RA, 1982, Rich TD, 1984, 1999, 2001).
Unlike typical antipsychotics - dopamine receptor antagonists (butyrophenone and phenothiazine derivatives), Eglonil is a benzamide derivative with selective blockade of dopamine receptors (Rich TD, 1984). Previously it was believed that Eglonil acts only on D2 receptors (Memo M, Battaini F, Spano PF et al, 1981, O'Connor SE, Brown RA, 1982), however, recent experimental data also indicate blockade of D3 and D4 dopamine receptors .(Caley CF, Weber SS, 1995). It is the effect on D2 and similar D4 receptors that is currently recognized as the basis of the antipsychotic effect of neuroleptics (Wilson JM, Sanyal S et al., 1998, Emilien G, Maloteaux JM, Geurts M et al., 1999). In addition, Eglonil has some effect on glutamate receptors, which affects its pharmacological properties (Herrera-Marschitz M, Stahle L, Tossman U et al., 1984). Eglonil does not affect adrenergic, cholinergic, histaminergic and serotonergic receptors, i.e. does not cause corresponding side effects. Eglonil has no active metabolites, and its elimination is carried out primarily through the kidneys. The absence of metabolism in the liver ensures that the drug does not have a negative effect on the liver. Due to predominant excretion in urine, Eglonil can accumulate in patients with severe renal failure (Barrett RJ, Ginos JZ, Lokhandwala MF, 1982, Caley CF, Weber SS, 1995, Mauri MC, Bravin S, Bitetto A et al., 1996) , which may cause side effects in these patients.
Despite the long-term use of Eglonil in clinical practice, there are few long-term placebo-controlled studies of the drug's effectiveness in the treatment of patients with mental disorders. The results of 18 studies presented in one of the latest reviews (Soares BG, Fenton M, Chue P, 2000) indicate its predominant effect on the negative symptoms of schizophrenia - apathy, lack of will, inhibition, autism. At the same time, many researchers emphasize the pronounced antipsychotic effect of Eglonil, prescribed in high doses (800–2800 mg/day),
aimed at productive symptoms (primarily delusions and hallucinations), not inferior to the most active antipsychotics. At the same time, however, in prolonged and severe psychotic states there is some benefit of treatment with haloperidol (at a dose of 6–18 mg/day) (Munk-Andersen E, Behnke K, Heltberg J et al., 1984). It has also been established that the effectiveness of treatment of psychosis increases with the combination of clozapine, which predominantly blocks dopamine D4 receptors, and Eglonil, which blocks D2 receptors (Shiloh R, Zemishlany Z, Aizenberg D et al., 1997), and in the most treatment-resistant cases, a combination is recommended Eglonil with olanzapine, another atypical antipsychotic that acts on serotonin 5HT2 receptors (Raskin S, Durst R, Katz G et al., 2000).
Compared with typical antipsychotics, in particular with haloperidol and chlorpromazine, Eglonil has a significant advantage due to the lower frequency and severity of unwanted and side effects
treatments, including extrapyramidal, anticholinergic and autonomic (Harnryd C, Bjerkenstedt L, Bjork K, et al., 1984, Mauri MC, Bravin S, Bitetto A, 1996).
However, with long-term treatment, especially in elderly patients, these effects are still possible. (Caley CF, Weber SS, 1995). Unlike most antipsychotics, Eglonil does not cause pronounced sedation
and inhibition, which provides the possibility of psychotherapeutic contact with the patient (Jenner P, Marsden CD, 1982).
An important advantage of the drug is the absence of hepatotoxicity
.
Studies of Eglonil conducted in healthy subjects did not reveal subjective and psychophysiological changes after a single dose of various doses of the drug. When studying reaction time, changes in heart rate and skin conductivity in response to various stimuli after administration of 100 mg of Eglonil, no differences were noted compared with placebo, which indicates the absence of a significant effect of small doses of Eglonil on mental and autonomic reactions (Barfai A, Wiesel FA, 1986). With the introduction of 300 mg of Eglonil, no subjective changes were also noted, in particular, there was no sedation
, however, a slight decrease in reaction time was detected (Meier-Lindenberg A, Ramsayer T, Ulferts J, et al. 1997).
Unlike most other antipsychotics, when treated with Eglonil, an increase in the level of prolactin in the blood plasma is observed - hyperprolactinemia (Rao VA, Bailey J, Bishop M et al., 1981, O'Connor SE, Brown RA, 1982).
The effect of Eglonil on prolactin production was studied at different therapeutic doses. It was noted that even in minimal doses, Eglonil significantly enhances the production of prolactin in healthy subjects (McMurdo ME, Hovie PW, Lewis M et al., 1987). In men, severe hyperprolactinemia can cause gynecomastia, as well as transient impotence and impaired ejaculation (Buvat J, Racadot A, Buvat-Herbaut M, 1997), however, these possible consequences of hyperprolactinemia, with the exception of gynecomastia, are not noted as side effects in any of the many clinical studies of Eglonil. In a number of studies conducted in small groups of women in the postpartum period, the use of Eglonil is proposed for the treatment of lactation deficiency
. As a result of treatment, a significantly greater increase in the weight of children whose mothers received Eglonil in small doses (150 mg/day) is indicated. At the same time, compared to the control group, women retained the possibility of breastfeeding for a longer time (Ylikorkala O, Kauppila A, Kivinen S et al., 1982). This effect was especially significant in women giving birth for the first time (Aono T, Aki T, Koike K et al., 1982), and also when compared with the effect of oxytocin (Ylikorkala O, Kauppila A, Kivinen S et al, 1984). At the same time, no side effects were detected in either mothers or children.
In recent years, along with extensive study of the involvement of norepinephrine and serotonin receptors in the pathogenesis of depressive spectrum disorders, there has been increasing interest in studying the role of the dopamine system. Thus, in one study of the sensitivity of dopamine receptors, a significantly more pronounced reaction of prolactin to the administration of Eglonil was revealed in depression, when compared with a healthy control group (Verbeeck WJ, Berk M, Paiker J et al., 2001). According to the authors, this fact indicates the involvement of the dopamine system in the pathogenesis of depression and suggests that this system may become a therapeutic target for depressive disorders.
It should be noted that almost all studies of the effectiveness of Eglonil emphasize significant differences in the clinical effects of low and high daily doses of the drug. The differences in the therapeutic targets of low and high doses of Eglonil are currently explained by their different pharmacological actions. Low doses, acting on presynaptic dopamine receptors and increasing dopamine neurotransmission, in addition to psychomotor stimulation
(Jenner P, Marsden CD, 1982),
have an antidepressant effect
(Vacceri A, Dall'Olio R, 1984, Benkert O, Holsboer F, 1984, Maier W, Benkert O 1994, Lestynek JL, 1983, Ruter E, Degner D, Munzel U, 1999),
anti-anxiety
(Meyers C, Vranckx C, Elgen K, 1985, Altamura AC, Mauri MC, Regazzetti G, 1990, Cavazzutti E, Bertlini A, Vergoni AV et al., 1999) and
analgesic
(Ferreri M, Florent C, Gerard D, 1998) effects.
Eglonil in medium and high doses, in addition to antagonism to presynaptic dopamine receptors, also exhibits antagonism to postsynaptic receptors, which affects the antipsychotic effect of the drug, characteristic of all neuroleptics - dopamine antagonists. However, the dual pre- and postsynaptic action of medium and high doses of Eglonil explains the lower severity of sedation and motor inhibition, compared with some other typical neuroleptics (Jenner P, Marsden CD, 1982, Mauri MC, Bravin S, Bitetto A et al., 1996, Drago F, Arezzi A, Virzi A, 2000). The table shows the results of some clinical and experimental studies of the effectiveness of low and high doses of Eglonil.
Considering the antipsychotic effect of medium and high doses of Eglonil, similar to other antipsychotics, the effect of the drug in small doses is of greatest interest from our point of view.
It is known that Eglonil in small therapeutic doses is currently actively used in the treatment of a wide range of depressive spectrum disorders, somatoform disorders,
as well as some functional somatic diseases, not only in specialized psychiatric, but also in general medical practice.
Clinical studies of Eglonil for depressive disorders have revealed its high effectiveness in some depressive disorders. However, most authors emphasized the individual and poorly predictable response to treatment. The antidepressant effect of Eglonil was largely associated with its psychostimulating effect, manifested primarily in a decrease in behavioral and motor symptoms of depression (Jenner P, Marsden CD, 1982) and in increased drives (Benkert O, Holsboer F, 1984), but even at the beginning There was no increase in accompanying anxiety symptoms during treatment. Among the negative properties of the drug, the authors noted the lack of a preventive effect during maintenance therapy. The study by Lestynek JL (1983) also noted that at a dose of 150 mg/day Eglonil primarily reduces psychomotor retardation, which was detected on the 5th day of treatment, and by the 10th day a clear antidepressant effect was observed in the majority (82%) of those examined patients
The high effectiveness of Eglonil was also found in chronic depression and dysthymia, with a positive effect on both the actual symptoms of depression and anxiety (Maier W, Benkert O, 1994). This seems to be one of the most important practical observations, since it confirms the effectiveness of Eglonil for prolonged anxious depression, which is most common today in general medical practice
(WHO, 2000). At the same time, however, the authors noted that the positive effect of Eglonil was quite individual and recommended conducting randomized placebo-controlled studies to identify clinical predictors of the drug’s effectiveness in chronic depression.
A large multicenter study of the antidepressant effect of Eglonil in 177 outpatients conducted in Germany (Ruther E, Degner D, Munzel U, et al., 1999) revealed a significant advantage of Eglonil at a dose of 150–300 mg/day when compared with placebo in the treatment of depression mild to moderate severity. The results of the study showed that undesirable effects occurred with a similar frequency in both groups, but they were more pronounced in the group of patients receiving placebo. Only 50% of patients with depression had an increase in prolactin levels above normal values. This study, in addition to the most important result - confirmation of the presence of an antidepressant effect, noted the safety of prescribing Eglonil in outpatient practice.
Studies of the effectiveness of Eglonil in somatoform disorders, which are often encountered not so much in psychiatric practice as in general medical practice, and are often difficult to treat, have revealed a positive effect of the drug associated with its multifaceted action.
In a comparative study of the effectiveness of Eglonil and flupenthixol in various somatoform disorders
, including psychogenic headaches, pain in the heart, functional disorders of the large intestine (Meyers C, Vranckx C, Elgen K, 1985), a positive effect was revealed within 4 weeks of treatment in 55 patients. However, there were no significant differences in the effectiveness and side effects of both drugs. When treating somatoform disorders with Eglonil, a rapid improvement in the condition of patients was noted, starting from the first week of treatment with a reduction in anxiety, hypochondriacal fixations and somato-vegetative disorders without significant side effects (Altamura AC, Mauri MC, Regazzetti G, 2000).
In a large multicenter study of the effectiveness of Eglonil for pain syndrome
(abdominal pain of a psychological nature in 669 patients), conducted in France (Ferreri M, Florent C, Gerard D, 2000), several positive effects of the drug were identified. During 6 weeks of treatment with Eglonil at a dose of 150 mg/day, 91% of patients experienced a significant reduction in pain intensity, and in 89%, the frequency of pain syndrome. In addition, along with a decrease in the severity of anxiety, the accompanying functional gastrointestinal symptoms also decreased - the motor function of the large intestine was normalized, nausea and vomiting were reduced, and appetite improved.
As an analysis of modern clinical studies of the effectiveness of Eglonil for depressive and somatoform disorders shows, despite the identification of some effects of the drug, identifying the specifics of its action requires further development. In this regard, consideration of the results of some experimental neuropsychological studies of the dopamine system can be used for clinical comparisons. In recent years, dopamine has been shown to be involved in forming connections between external stimuli and subsequent reward or frustration. Activation of the dopamine system promotes learning to recognize natural stimuli and identify incentives that cause desires (Schultz W., 1997, Spanagel R., Weiss F., 1999). At the same time, however, this system does not affect hedonism - receiving pleasure and thus is not associated with the pathogenesis of anhedonia - one of the central signs of typical depression (Berridge KC, Robinson TE, 1998). Based on these results, it can be assumed that disruption of dopamine metabolism leads to a decrease in motivation, that is, to the development of atypical symptoms of the apathetic range. Therefore, apparently, Eglonil exhibits the most pronounced antidepressant effect in small therapeutic doses in apathetic and anxious-apathetic depression
, in which a decrease in motivation and drive, accompanied by somatoform hypochondriacal and conversion symptoms, is the basis of the disorder.
Experimental psychophysiological studies of depression have provided indirect confirmation of these observations. It turned out that the antidepressant effect of Eglonil in small doses manifests itself primarily at the behavioral level in the form of increased activity. However, zglonil has no effect on behavior in other experimental models of depression (Vaccheri A, Dall'Ollo R, Gaggi R et al., 1984, Vergoni AV, Forgione A, Bertolini A, 1995, Drago F, Arezzi A, Virzi A, 2000).
Another indirect confirmation is a study of the effect of Eglonil (100 mg), bromocriptine and placebo on EEG (Fm-theta activity) and the severity of anxiety, conducted in 24 healthy students (Mizuki Y. Suetsugi M, Ushijima I et al., 1997). This study allowed the authors to suggest that the sensitivity of presynaptic dopamine D2 receptors (the therapeutic “target” of small, antidepressant doses of Eglonil) depends on personal anxiety. This sensitivity turned out to be significantly higher in anxious individuals, and the anti-anxiety effect of the drug was associated with a decrease in receptor activity. With low personal anxiety, which is typical, in particular, for patients with apathetic depression, a decrease in the sensitivity of D2 receptors was noted, and the anti-anxiety effect of small doses of Eglonil was associated with its increase. These results have not been confirmed in other studies, in particular in clinical studies, but they stimulate further searches for individual factors predicting the effectiveness of treatment for depressive and anxiety disorders of different pathogenesis.
Positive effect of Eglonil in somatoform disorders, especially when symptoms are localized in the gastrointestinal tract
, is explained by the blockade of not only central dopamine receptors, which leads to a decrease in symptoms of anxiety and depressive symptoms, but also peripheral receptors, which affects the normalization of the motor activity of the stomach, intestines and gall bladder (Barrett RJ, Ginos JZ, Lokhandwala MF, 1982, Guslandi M ,1990). It has also been shown that Eglonil, like other anti-dopamine drugs, significantly reduces the secretory function of the stomach, but does not affect basal or stimulated gastric acidity. This effect has been used with varying success in the treatment of gastric ulcers (Caldara R, Masci E, Cambielli M et al., 1983, 2000).
As the results of a number of studies have shown, the peripheral effect of Eglonil on dopamine receptors can be widely used for organic and functional dyspepsia, gastroduodenitis, hepatitis, as well as for the prevention of nausea and vomiting during chemotherapy and in the preoperative period (Guslandi M, 1990, Cohen N, Alon I , Almoznino–Sarfian D et al., 1999).
Study of the effectiveness of levosulpiride
(one of the isomers of Eglonil (sulpiride), which has greater peripheral activity) for functional dyspepsia, was carried out by Italian gastroenterologists (Corazza GR, Biagi F, Albano O et al, 2000). During 4 weeks of treatment of a large group of patients, normalization of gastrointestinal motility, reduction of nausea and vomiting, intestinal bloating, regurgitation, and epigastric pain were noted. Undesirable effects of therapy in the form of galactorrhea and menstrual irregularities were quite rare.
Of particular note is the study of the effectiveness of levosulpiride in diabetic gastric paresis (Mansi C, Savarino V, Vigneri S et al., 1995) and gallbladder (Mansi C, Savarino V, Vigneri et al. 1995). It is known that with chronic hyperglycemia, the mobility of the stomach and gallbladder is significantly affected. Based on the positive results of the study, the authors note that by normalizing the mobility of the stomach and gallbladder during treatment with levosulpiride, better control of blood sugar concentrations is achieved. Similar results confirming increased motor activity of the gallbladder were obtained when Eglonil was prescribed for duodenal ulcers (Szabelska K, Chojnacki J, Grzegorczyk et al., 1999).
Thus, the various clinical effects of Eglonil (sulpiride) are explained by the following reasons:
1. Selective blockade of dopamine (D2 D3 and D4) receptors, which determines its specific properties as an atypical antipsychotic with minimal side and undesirable effects.
2. Different effects of small (50–300 mg/day) and higher (300–3200 mg/day) doses of Eglonil on presynaptic and postsynaptic dopamine receptors. This difference explains the manifestation of the atypical antidepressant, anti-anxiety or anxiolytic (low doses) and atypical neuroleptic (high doses) effect of Eglonil.
3. Both central and peripheral blockade of dopamine receptors.
The presence of a peripheral effect of the drug on dopamine receptors explains its effectiveness in some somatoform as well as functional somatic diseases of the gastrointestinal tract. References:
1. O'Connor SE, Brown RA. The pharmacology of sulpiride – a dopamine receptor antagonist. Gen. Pharmacol., 1982, 13, 185–193
2. Rich TD. Sulpiride: assessment of a pharmacologically and chemically distinct neuroleptic. Med. Hypotheses, 1984, 5, 14, 69–81
3. Memo M, Battaini F, Spano PF et al. Sulpiride and the role of dopaminergic receptor blockade in the antipsychotic activity of neuroleptics. Acta Psychiatr. Scand.,1981, 4, 63, 314–324
4. Caley CF, Weber SS. Sulpiride: an antipsychotic with selective dopaminergic antagonist properties. Ann Pharmacother., 1995, 2, 29, 152–160
5. Wilson JM, Sanyal S, Van Tol H. Dopamine D2 and D4 receptor ligands: relation to antipsychotic action. Eur. J. Pharmacol., 1998, 351, 3, 273–286
6. Emilien G, Maloteaux JM, Geurts M et al. Dopamine receptors – physiological understanding to therapeutic intervention. Pharmacol and Therapeutics, 1999, 84, 2, 133–156
7. Herrera–Marschitz M, Stahle L, Tossman U et al. Behavioral and biochemical studies with the benzamide sulpiride in rats. Acta Psychiatr. Scand. Suppl, 1984, 311, 147–162
8. Barrett RJ, Ginos JZ, Lokhandwala MF, Evaluation of peripheral dopamine receptor and alpha-adrenoceptor blocking activity of sulpiride. Eur. J. Pharmacol., 1982, 4, 79, 273–281
9. Mauri MC, Bravin S, Bitetto A et al. A risk–benefit assessment of sulpiride in the treatment of schizophrenia. Drug Saf., 1996, 5, 14, 288–298
10. Soares BG, Fenton M, Chue P. Sulpiride for schizophrenia. Cohrane Database Syst.Rev., 2000, Issue 2
11. Munk–Andersen E, Behnke K, Heltberg J et al. Sulpiride versus haloperidol, a clinical trial in achizophrenia. A preliminary report. Acta Psychiatr. Scand. Suppl., 1984, 311, 31–41
12. Shiloh R, Zemislany Z, Aizenberg D et al. Sulpiride augmentation in people with schizophrenia partially responsive to clozapine. A double-blind, placebo-controlled study. Br. J. Psychiatry, 1997, 12, 171, 569–573
13. Raskin S, Durst R, Katz G et al. Olanzapine and sulpiride: a preliminary study of combination/augmentation in patients with treatment–resistant achizophrenia. J. Clin. Psychopharmacol., 2000, 20, 500–503
14. Harnryd C, Bjerkenstedt L, Bjork K, et al. Clinical evaluation of sulpiride in schizophrenic patients – a double–blind comparison with chlorpromazine. Acta Psychiatr. Scand. Suppl., 1984, 311, 7–30
15. Jenner P, Marsden CD. The mode of action of sulpiride as an atypical antidepressant agent. Adv. Biochem. Psychopharmacol., 1982, 32, 85–103
16. Barfai A, Wiesel FA. Effect of sulpiride on vigilance in healthy subjects. Int.J.Psychophysiol., 1986, 4, 1–5
17. Meier–Lindenberg A, Rammsayer T, Ulferts J et al. The effect of sulpiride on psychomotor performance and subjective tolerance. Eur. Neuropsychopharmacol., 1997, 7, 219–223
18. Rao VA, Bailey J, Bishop M et al., A clinical and pharmacodynamic evaluation of sulpiride. Psychopharmacology, 1981, 73, 77–80
19. McMurdo ME, Hovie PW, Lewis M et al. Prolactin response to low dose sulpiride. Br.J. Clin. Pharmacol. , 1987, 8, 24, 133–137
20. Buvat J, Racadot A, Buvat–Herbaut M. Basal prolactinaemia and responses to TRH and to sulpiride in different categories of male sexual dysfunctions. Acta Psychiatr. Belg., 1997, 80, 487–493
21. Ylikorkala O, Kauppila A, Kivinen S et al. Sulpiride improves inadequate lactation. Br. Med. J., 1982, 7, 285, 249–251
22. Aono T, Aki T, Koike K et al. Effect of sulpiride on poor puerperal lactation. Am.J. Obstet. Gynecol., 1982, 8, 143, 927–932
23. Ylikorkala O, Kauppila A, Kivinen S et al. Treatment of inadequate lactation with iral sulpiride and buccal oxytocin. Obstet. Gynecol 1984, 1, 63, 57–60
24. Verbeeck WJ, Berk M, Paiker J et al. The prolactin response to sulpiride in major depression: the role of the D(2) receptor in depression. Eur. Neuropsychopharmacol., 2001, 6, 11, 215–220
25. Vacceri A, Dall'Olio R, Gaggi R, et al. Antidepressant versus neuroleptic activities of sulpiride isomers on four animal models of depression. Psychopharmacology (Berl), 1984, 83, 28–33
26. Benkert O, Holsboer F. Effect of sulpiride in endogenous depression. Acta Psychiatr. Scand. Suppl, 1984, 311, 43–48
27. Maier W, Benkert O, Treatment of chronic depression with sulpiride: evidence of efficacy in placebo–controlled single case studies. Psychopharmacology (Berl), 1994, 8, 115, 495–501
28. Lestynek JL. Sulpiride and depression. Sem. Hop., 1983, 59, 2354–2357
29. Ruter E, Degner D, Munzel U. Antidepressant action of sulpiride. Results of a placebo–controlled double–blind trial. Pharmacopsychiatry, 1999, 32,127–135
30. Meyers C, Vranckx C, Elgen K. Psychosomatic disorders in general practice: comparisons of treatment with flupentixol, diazepam and sulpiride. Pharmacotherapeutica, 1985, 4, 244–250
31. Altamura AC, Mauri MC, Regazzetti G. L–sulpiride in the treatment of somatoform disturbances: a double–blind study with racemic sulpiride. Minerva Psichiatr., 2000, 32, 25–29
32. Cavazzutti E, Bertlini A, Vergoni AV et al. L–Sulpiride at a low, non–neuroleptic dose, prevents conditioned fear stress–induced fresco behavior in rats. Psychopharmacology (Berl), 1999, 3, 143, 20–23
33. Ferreri M, Florent C, Gerard D, Sulpiride: study of 669 patient presenting with pain psychological origin. Encephale, 2000, 26, 58–66
34. Drago F, Arezzi A, Virzi A. Effects of acute or chronic administration of substituted benzamides in experimental models of depression in rats. Eur. Neuropsychopharmacology, 2000, 10, 437–442
35. WHO Guide to Mental Health in Primary Care. London: Royal Society of Medicine Press, 2000
36. Schultz W. Dopamine neurons and their role in reward mechanisms. Current Opinion in Neurobiology, 1997, 7, 191–197
37. Spanagel R., Weiss F. The dopamine hypothesis of reward: past and current status. Trends in Neurosciences, 1999, 22, 521–527
38. Berridge KC, Robinson TE. What is the role of dopamine in reward: hedonic impact, reward learning or ince salience? Brain Res.Rev,1998, 28, 3, 309–369
39. Vergoni AV, Forgione A, Bertolini A. Chronic administration of I-sulpiride at non-neuroleptic doses reduces the duration of immobility in experimental models of “depression-like” behavior. Psychopharmacology (Berl), 1995, 121, 279–281
40. Mizuki Y, Suetsugi M, Ushijima I et al. Differential effects of dopaminergic drugs on anxiety and arousal in healthy volunteers with high and low anxiety. Prog. Neuropsychopharmacol. Biol. Psychiatry, 1997, 21, 573–590
41. Guslandi M. Antiemetic properties of levo-sulpiride. Minerva Med., 1990, 12, 81, 855–860
42. Caldara R, Masci E, Cambielli M et al. Effect of sulpiride isomers on gastric acid and gastrin secretion in healthy man. Eur. J. Clin. Pharmacol., 1983, 25, 319–322
43. Cohen N, Alon I, Almoznino–Sarfian D et al. Sulpiride versus metoclopramide in nononcologic patiets with vomiting and nausea. J.Clin. Gastroenterol.1999, 7, 29, 59–62
44. Corazza GR, Biagi F, Albano O et al. Levosulpiride in functional dyspepsia: a multicentric, double–blind, controlled trial. Ital. J. Gastroenterol., 2000, 28, 317–323
45. Mansi C, Savarino V, Vigneri S et al. Gastrocinetic effects of levosulpiride in dyspeptic patients with diabetic gastroparesis. Am.J. Gastroenterol., 1995, 11, 90, 1989–1993
46. Mansi C, Savarino V, Vigneri S et al. Effect of D2–dopamine raceptor antagonist levosulpiride on diabetic cholecystoparesis: a double–blind crossover study. Aliment. Pharmacol. Ther., 1995, 4, 9, 185–189
47. Szabelska K, Chojnacki J, Grzegorczyk J et al. Effect of procinetic drugs inhibiting dopaminergic system on gallbladder motility in subjects with duodenal ulcer. Pol. Merkuriusz. Lek., 1999, 6, 188–191
48. Pich EM, Samanin R., Disinhibitory effects of buspirone and low doses of sulpiride and haloperidol in two experimental anxiety models in rats: possible role of dopamine. Psychopharmacology (Berl), 1986, 89, 125–130
Use of the drug Eglonil
Initial treatment is carried out with intramuscular administration of the drug, after which it is switched to oral administration. For neurotic, psychofunctional and psychoaffective disorders associated with somatic conditions: Adults - 100–200 mg/day. Children over 6 years of age: 5 mg/kg body weight per day (if necessary, this dose can be increased to 10 mg/kg). In acute and chronic psychosis, the dose is set in accordance with the prevailing symptoms: negative - 200-600 mg/day, positive - 800-1600 mg/day.
pharmachologic effect
Sulpiride is an atypical antipsychotic from the group of substituted benzamides.
Sulpiride has moderate neuroleptic activity in combination with stimulating and thymoanaleptic (antidepressive) effects.
The neuroleptic effect is associated with an antidopaminergic effect. In the central nervous system, sulpiride predominantly blocks dopaminergic receptors of the limbic system, and has a slight effect on the neostriatal system; it has an antipsychotic effect. The peripheral effect of sulpiride is based on inhibition of presynaptic receptors. An increase in the amount of dopamine in the central nervous system is associated with an improvement in mood, and a decrease is associated with the development of symptoms of depression.
The antipsychotic effect of sulpiride is manifested in doses of more than 600 mg/day; in doses of up to 600 mg/day, the stimulating and antidepressant effect predominates.
Sulpiride does not have a significant effect on adrenergic, cholinergic, serotonin, histamine and GABA receptors.
In small doses, sulpiride can be used as an additional remedy in the treatment of psychosomatic diseases; in particular, it is effective in relieving the negative mental symptoms of gastric and duodenal ulcers. In irritable bowel syndrome, sulpiride reduces the intensity of abdominal pain and leads to an improvement in the patient's clinical condition.
Low doses of sulpiride (50-300 mg/day) are effective for dizziness, regardless of etiology. Sulpiride stimulates the secretion of prolactin and has a central antiemetic effect (suppression of the vomiting center) due to the blockade of dopamine D2 receptors in the trigger zone of the vomiting center.
Side effects of the drug Eglonil
Sedation, drowsiness, early dyskinesia (spasmodic torticollis, oculogyric crises, trismus, which decrease with the administration of anticholinergic antiparkinsonian drugs), extrapyramidal symptoms, the severity of which partially decreases with the administration of anticholinergic antiparkinsonian drugs, tardive dyskinesia, which develops with long-term use of antipsychotics (anticholinergic antiparkinsonian drugs are ineffective and can worsen the patient’s condition), postural hypotension, impotence, frigidity, amenorrhea, galactorrhea, gynecomastia, hyperprolactinemia, weight gain.
Drug interactions
Contraindicated combinations
Dopaminergic receptor agonists (amantadine, apomorphine, bromocriptine, cabergoline, entacapone, lisuride, pergolide, piribedil, pramipexole, kinagolide, ropinirole), except for patients suffering from Parkinson's disease:
There is mutual antagonism between dopaminergic receptor agonists and antipsychotics. For extrapyramidal syndrome induced by antipsychotics, dopaminergic receptor agonists are not used; in such cases, anticholinergics are used.
Sultopride:
the risk of ventricular arrhythmias, in particular atrial fibrillation, increases.
Combinations not recommended
Drugs that can cause ventricular arrhythmias: antiarrhythmic drugs of class Ia (quinidine, hydroquinidine, disopyramide) and class III (amiodarone, sotalol, dofetilide, ibutilide), some antipsychotics (thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, amisulpride, tiapride, haloperidol, droperidol, pimozide) and other drugs such as: bepridil, cisapride, difemanil, intravenous erythromycin, mizolastine, intravenous vincamine, etc.
Ethanol:
enhances the sedative effect of neuroleptics. Impaired attention creates a danger for driving vehicles and working on machines. The consumption of alcoholic beverages and the use of medications containing ethyl alcohol should be avoided.
Levodopa:
mutual antagonism is observed between levodopa and antipsychotics. Patients suffering from Parkinson's disease should be prescribed the minimum effective dose of both drugs.
Dopaminergic receptor agonists (amantadine, apomorphine, bromocriptine, cabergoline, entacapone, lisuride, pergolide, piribedil, pramipexole, kinagolide, ropinirole), in patients suffering from Parkinson's disease:
There is mutual antagonism between dopaminergic receptor agonists and antipsychotics. The above drugs may cause or worsen psychosis. If treatment with an antipsychotic is necessary for a patient suffering from Parkinson's disease and receiving a dopaminergic antagonist, the dose of the latter should be gradually reduced until discontinuation (abrupt withdrawal of dopaminergic agonists can lead to the development of neuroleptic malignant syndrome).
Halofantrine, pentamidine, sparfloxacin, moxifloxacin:
the risk of ventricular arrhythmias, in particular “torsade de pointes”, increases. If possible, the antimicrobial drug causing ventricular arrhythmia should be discontinued. If the combination cannot be avoided, the QT interval should first be checked and ECG monitoring should be ensured.
Combinations requiring caution
Drugs that cause bradycardia (calcium channel blockers with bradycardic action: diltiazem, verapamil, beta-blockers, clonidine, guanfacine, digitalis alkaloids, cholinesterase inhibitors: donepezil, rivastigmine, tacrine, ambenonium chloride, galantamine, pyridostigmine, neostigmine):
the risk of ventricular arrhythmias, in particular “torsade de pointes”, increases. Clinical and ECG monitoring is recommended.
Drugs that reduce potassium levels in the blood (potassium-sparing diuretics, stimulant laxatives, amphoteric B (iv), glucocorticoids, tetracosactide):
the risk of ventricular arrhythmias, in particular “torsade de pointes”, increases. Before prescribing the drug, hypokalemia should be eliminated and clinical, cardiographic monitoring, as well as monitoring of electrolyte levels, should be established.
Combinations to consider:
Antihypertensive drugs:
enhancing the hypotensive effect and increasing the possibility of postural hypotension (additive effect).
Other CNS depressants:
morphine derivatives (analgesics, antitussives and replacement therapy), barbiturates, benzodiazepines and other anxiolytics, hypnotics, sedative antidepressants, sedative histamine H1 receptor antagonists, centrally acting antihypertensives, baclofen, thalidomide - central nervous system depression, impaired attention creates a danger for driving. and working on machines.
Sucralfate, antacids containing Mg2+ and/or A13+, reduce the bioavailability of oral dosage forms by 20-40%. Sulpiride should be prescribed 2 hours before taking them.
Special instructions for the use of the drug Eglonil
If hyperthermia develops, sulpiride should be discontinued. Hyperthermia may be a manifestation of neuroleptic malignant syndrome (pallor, hyperthermia and autonomic dysfunction). This precaution is especially important when using the drug in high doses. Caution should be exercised when treating elderly patients who are more susceptible to the effects of the drug. Since sulpiride is excreted by the kidneys, in patients with severe renal failure the drug should be used in reduced doses and an intermittent treatment regimen should be used. Patients with epilepsy require more careful monitoring (clinical and, if necessary, EEG), since sulpiride reduces the seizure threshold. In patients with Parkinson's disease, sulpiride is prescribed with caution according to strict indications. In patients with aggressive behavior or agitation with impulsivity, sulpiride should be prescribed together with sedatives. In children whose mothers took low doses of sulpiride (approximately 200 mg/day) during pregnancy, no increase in the incidence of birth defects was observed. There is no experience with using the drug in higher doses. There is also no data on the potential effect of antipsychotic drugs taken during pregnancy on fetal brain development. It seems advisable, if possible, to reduce the dose and reduce the duration of treatment with the drug during pregnancy. In newborns whose mothers underwent long-term treatment with antipsychotics in high doses, several cases of the development of extrapyramidal syndrome have been described. It is recommended to monitor the neurological status of children born to mothers receiving the drug for some time after birth. Since sulpiride passes into breast milk, breastfeeding should be discontinued during treatment with the drug. Drivers of vehicles and persons working with potentially dangerous mechanisms should be warned about the possibility of developing drowsiness while taking the drug.
Contraindications
- prolactin-dependent tumors (for example, pituitary prolactinomas and breast cancer);
- hyperprolactinemia;
- acute intoxication with ethanol, hypnotics, opioid analgesics;
— affective disorders, aggressive behavior, manic psychosis;
- pheochromocytoma;
- period of breastfeeding;
- children under 18 years of age (for tablets and solution for intramuscular administration);
- children under 6 years of age (for capsules);
- in combination with sultopride, dopaminergic receptor agonists (amantadine, apomorphine, bromocriptine, cabergoline, entacapone, lisuride, pergolide, piribedil, pramipexole, kinagolide, ropinirole);
- hypersensitivity to sulpiride or another ingredient of the drug.
Due to the presence of lactose in the drug, it is contraindicated in congenital galactosemia, glucose/galactose malabsorption syndrome or lactase deficiency.
Carefully:
It is not recommended to prescribe sulpiride to pregnant women, except in cases where the doctor, having assessed the balance of benefit and risk for the pregnant woman and the fetus, decides that the use of the drug is necessary.
It is not recommended to prescribe sulpiride in combination with ethanol, levodopa, drugs that can cause ventricular arrhythmias (antiarrhythmic drugs of class 1a (quinidine, hydroquinidine, disopyramide) and class III (amiodarone, sotalol, dofetilide, ibutilide)), some neuroleptics (thioridazein, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, amisulpride, tiapride, pimozide, haloperidol, droperidol) and other drugs such as: bepridil, cisapride, difemanil, intravenous erythromycin, mizolastine, intravenous vincamine, halofantrine, pentamidine, sparfloxacin, moxifloxacin, etc.
Precautions must be taken when prescribing sulpiride to patients with renal and/or liver failure, a history of neuroleptic malignant syndrome, a history of epilepsy or seizures, severe heart disease, arterial hypertension, patients with parkinsonism, dysmenorrhea, and the elderly.
Interactions of the drug Eglonil
Alcohol can potentiate the sedative effect of antipsychotic drugs, therefore, during treatment with sulpiride, patients should refrain from drinking alcohol and using medications containing ethyl alcohol. Levodopa has an antagonistic effect relative to antipsychotic drugs and vice versa. Patients with extrapyramidal symptoms due to the use of antipsychotic drugs should not be prescribed levodopa. If an antipsychotic drug is required in a patient taking levodopa for Parkinson's disease, it is recommended to choose a drug with mild extrapyramidal effects, in particular chlorpromazine or levomepromazine. Antihypertensive drugs may have additive hypotensive effects and increase the risk of postural hypotension. Drugs that cause central nervous system depression (morphine derivatives, most H1 receptor blockers, barbiturates, benzodiazepines, non-benzodiazepine tranquilizers, clonidine and related compounds) potentiate the depressing effect of sulpiride.
Dosage
Solution for intramuscular administration
For acute and chronic psychoses
Treatment begins with intramuscular injections at a dose of 400-800 mg/day and is continued in most cases for 2 weeks. The goal of therapy is to achieve the minimum effective dose.
When administering sulpiride intramuscularly, the usual rules for intramuscular injections are followed: deep into the outer upper quadrant of the gluteal muscle, the skin is pre-treated with an antiseptic.
Depending on the clinical picture of the disease, intramuscular injections of sulpiride are prescribed 1-3 times a day, which can quickly alleviate or stop symptoms. As soon as the patient's condition allows, you should proceed to taking the drug orally. The course of treatment is determined by the doctor.
Tablets and capsules
Take 1-3 times a day with a small amount of liquid, regardless of meals.
The goal of therapy is to achieve the minimum effective dose.
It is not recommended to take the drug in the afternoon (after 16:00) due to an increase in activity level.
Pills
Acute and chronic schizophrenia, acute delirious psychosis, depression:
the daily dose is from 200 to 1000 mg, divided into several doses.
Capsules
Neuroses and anxiety in adults
patients:
the daily dose is from 50 to 150 mg for a maximum of 4 weeks.
Severe behavioral disorders in children
:
daily dose is from 5 to 10 mg/kg body weight.
Doses for the elderly:
The initial dose of sulpiride should be 1/4-1/2 the dose for adults.
Doses in patients with renal impairment
Due to the fact that sulpiride is excreted from the body primarily through the kidneys, it is recommended to reduce the dose of sulpiride and/or increase the interval between the administration of individual doses of the drug depending on the QC indicators:
| CC (ml/min) | Dose of Sulpiride compared to standard (%) | Increasing the interval between doses of Sulpiride |
| 30-60 ml/min | 70 | 1.5 times |
| 10-30 ml/min | 50 | 2 times |
| less than 10 ml/min | 30 | 3 times |
Overdose of the drug Eglonil, symptoms and treatment
Dyskinetic manifestations with spastic torticollis, tongue protrusion and trismus. Some patients sometimes develop severe manifestations of parkinsonism and coma. Eglonil is partially excreted during hemodialysis. Treatment is symptomatic: resuscitation measures, intensive care with constant monitoring of breathing and cardiac activity (with an increase in the Q-T ), which must be carried out until the patient’s complete recovery. If severe extrapyramidal symptoms develop, anticholinergic drugs should be used.
