cyproheptadine

Summary

Summary: A serotonin antagonist and a histamine H1 blocker used as antipruritic, appetite stimulant, antiallergic, and for the post-gastrectomy dumping syndrome, etc.

Top Publications

  1. Katiyar S, Prakash S. Pharmacological profile, efficacy and safety of rupatadine in allergic rhinitis. Prim Care Respir J. 2009;18:57-68 pubmed publisher
    ..Rupatadine significantly improves nasal symptoms in patients with AR. It has a good safety profile and is devoid of arrythmogenic effects. These properties make rupatadine a suitable first line anti-histamine for the treatment of AR. ..
  2. Paoluzzi L, Scotto L, Marchi E, Seshan V, O Connor O. The anti-histaminic cyproheptadine synergizes the antineoplastic activity of bortezomib in mantle cell lymphoma through its effects as a histone deacetylase inhibitor. Br J Haematol. 2009;146:656-9 pubmed publisher
    b>Cyproheptadine, an inhibitor of the H1 histamine receptors, has recently shown activity in models of leukaemia and myeloma, presumably through inhibition of cyclin-D expression...
  3. Casulari L, Naves L, Mello P, Pereira Neto A, Papadia C. Nelson's syndrome: complete remission with cabergoline but not with bromocriptine or cyproheptadine treatment. Horm Res. 2004;62:300-5 pubmed
    ..The patient was initially treated with cyproheptadine hydrochloride (12 mg/day) for 18 months...
  4. Hawkins B, Fischer L. Inhibition of insulin synthesis by cyproheptadine: effects on translation. Toxicol Sci. 2004;79:258-65 pubmed
    The antihistaminic, antiserotonergic drug cyproheptadine (CPH) is known to inhibit insulin synthesis in vivo and in vitro...
  5. Donado E, Izquierdo I, Pérez I, García O, Antonijoan R, Gich I, et al. No cardiac effects of therapeutic and supratherapeutic doses of rupatadine: results from a 'thorough QT/QTc study' performed according to ICH guidelines. Br J Clin Pharmacol. 2010;69:401-10 pubmed publisher
    ..This 'thorough QT/QTc study' confirmed previous experience with rupatadine and demonstrated that it had no proarrhythmic potential and raised no concerns regarding its cardiac safety. ..
  6. Baigel G. Cyproheptadine and the treatment of an unconscious patient with the serotonin syndrome. Eur J Anaesthesiol. 2003;20:586-8 pubmed
  7. Metz M, Maurer M. Rupatadine for the treatment of allergic rhinitis and urticaria. Expert Rev Clin Immunol. 2011;7:15-20 pubmed publisher
    ..Here, we review the profile of rupatadine, a new dual platelet-activating factor and H1-receptor antagonist that fulfils these criteria and therefore offers an excellent option for the treatment of allergic diseases. ..
  8. Mao X, Liang S, Hurren R, Gronda M, Chow S, Xu G, et al. Cyproheptadine displays preclinical activity in myeloma and leukemia. Blood. 2008;112:760-9 pubmed publisher
    ..we conducted a high throughput screen for inhibitors of the cyclin D2 promoter and identified the drug cyproheptadine. In myeloma and leukemia cells, cyproheptadine decreased expression of cyclins D1, D2, and D3 and arrested ..
  9. Codd E, Baker J, Brandt M, Bryant S, Cai C, Carson J, et al. Diabetogenic effect of a series of tricyclic delta opioid agonists structurally related to cyproheptadine. Toxicol Sci. 2010;117:493-504 pubmed publisher
    ..A review of the literature on the antiserotonergic and antihistaminergic drug cyproheptadine (CPH) and its metabolites revealed shared structural features as well as similar hyperglycemic effects to the ..

More Information

Publications62

  1. Suh H, Chung K, Kim Y, Huh S, Song D. Effects of histamine receptor antagonists injected intrathecally on antinociception induced by opioids administered intracerebroventricularly in the mouse. Neuropeptides. 1999;33:121-9 pubmed
    ..The effects of intrathecal (i.t.) injections with cyproheptadine [a histamine-1 (H1) receptor antagonist], ranitidine (a H2 receptor antagonist), or thioperamide (a H3 ..
  2. Goudie A, Cooper G, Cole J, Sumnall H. Cyproheptadine resembles clozapine in vivo following both acute and chronic administration in rats. J Psychopharmacol. 2007;21:179-90 pubmed
    b>Cyproheptadine is a cheap, widely available anti-allergy drug with a broad receptor binding profile which resembles that of clozapine. In rats discriminating clozapine from vehicle cyproheptadine mimicked clozapine very closely...
  3. Donaldson M, LaMonte B, Morresey P, Smith G, Beech J. Treatment with pergolide or cyproheptadine of pituitary pars intermedia dysfunction (equine Cushing's disease). J Vet Intern Med. 2002;16:742-6 pubmed
    Medical records of 27 horses (including 13 ponies) treated with pergolide or cyproheptadine for pituitary pars intermedia dysfunction were reviewed to determine the effect of treatment on plasma ACTH, insulin, and glucose concentrations ..
  4. Hargrove V, Molina D. A fatality due to cyproheptadine and citalopram. J Anal Toxicol. 2009;33:564-7 pubmed
    b>Cyproheptadine (Periactin) is a first-generation antihistamine available in over-the-counter cold medications and is used to treat allergic-type symptoms...
  5. Dabaghzadeh F, Ghaeli P, Khalili H, Alimadadi A, Jafari S, Akhondzadeh S, et al. Cyproheptadine for prevention of neuropsychiatric adverse effects of efavirenz: a randomized clinical trial. AIDS Patient Care STDS. 2013;27:146-54 pubmed publisher
    b>Cyproheptadine prevention of the neuropsychiatric adverse effects of an antiretroviral regimen including efavirenz has been evaluated in a randomized clinical trial...
  6. Picado C. Rupatadine: pharmacological profile and its use in the treatment of allergic disorders. Expert Opin Pharmacother. 2006;7:1989-2001 pubmed
    ..Rupatadine does not present drug-drug interactions with azithromycin, fluoxetine and lorazepam, but should not be administered concomitantly with known CYP3A4 inhibitors. ..
  7. Saveika J, Shelton J. Cyproheptadine for pediatric intrathecal baclofen withdrawal: a case report. Am J Phys Med Rehabil. 2007;86:994-7 pubmed
    ..Previous reports have documented use of cyproheptadine in treatment of this syndrome in adults with positive results...
  8. Droogmans S, Roosens B, Cosyns B, Degaillier C, Hernot S, Weytjens C, et al. Cyproheptadine prevents pergolide-induced valvulopathy in rats: an echocardiographic and histopathological study. Am J Physiol Heart Circ Physiol. 2009;296:H1940-8 pubmed publisher
    ..Therefore, we sought to determine whether cyproheptadine, a 5-HT(2B)R antagonist, might prevent toxic valvulopathy in an animal model of pergolide-induced valvular ..
  9. Tanaka Y, Makiyama Y, Mitsui Y. Anti-CD44 monoclonal antibody (IM7) induces murine systemic shock mediated by platelet activating factor. J Autoimmun. 2002;18:9-15 pubmed
    ..This study describes potential triggering pathways for shock that must be avoided through modification of the immunotherapy. ..
  10. Zafonte R, Lombard L, Elovic E. Antispasticity medications: uses and limitations of enteral therapy. Am J Phys Med Rehabil. 2004;83:S50-8 pubmed
  11. Wang L, Zhang Q, Hu X, Lun N, Zhu F. Verapamil, cyproheptadine, and anisodamine antagonized [Ca2+]i elevation induced by TNFalpha in a single endothelial cell. Acta Pharmacol Sin. 2001;22:918-22 pubmed
    ..factor alpha (TNFalpha) on intracellular free Ca2+ concentration ([Ca2+]i) and the effects of verapamil (Ver), cyproheptadine (Cyp), and anisodamine (Ani) on TNFalpha-induced [Ca2+]i changes in single endothelial cell, and to explore ..
  12. Zhou S, Kestell P, Tingle M, Ching L, Paxton J. A difference between the rat and mouse in the pharmacokinetic interaction of 5,6-dimethylxanthenone-4-acetic acid with thalidomide. Cancer Chemother Pharmacol. 2001;47:541-4 pubmed
    Coadministration of thalidomide, cyproheptadine or diclofenac has been shown to increase the area under the plasma concentration-time curve (AUC) of the novel antitumour agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in mice...
  13. Majczynski H, Cabaj A, Górska T. Intrathecal application of cyproheptadine impairs locomotion in intact rats. Neurosci Lett. 2005;381:16-20 pubmed
    In intact adult rats, cyproheptadine, a 5-HT2 antagonist, administered intrathecally at the midlumbar segments was found to impair hindlimb locomotor movements during overground locomotion...
  14. Daviss W, Scott J. A chart review of cyproheptadine for stimulant-induced weight loss. J Child Adolesc Psychopharmacol. 2004;14:65-73 pubmed
    ..b>Cyproheptadine has been shown in medical samples to stimulate weight gain...
  15. Mancilla Díaz J, Escartín Pérez R, López Alonso V. The effects of 5-HT on feeding behaviour in mianserin- or cyproheptadine-pretreated rats. Eat Weight Disord. 2003;8:268-73 pubmed
    ..on the feeding behaviour patterns of rats pretreated with mianserin (5-HT(1B/2A/1D receptor antagonist) or cyproheptadine (a 5-HT(2c) receptor antagonist), injected into the pariventricular hypothalamus nucleus (PVN)...
  16. Singh D, Goel R. Anticonvulsant effect of Ficus religiosa: role of serotonergic pathways. J Ethnopharmacol. 2009;123:330-4 pubmed publisher
    ..p.) was studied in seizures induced by maximum electroshock (MES), picrotoxin and pentylenetetrazol (PTZ). Cyproheptadine, a nonselective (5HT(1/2)) serotonin antagonist (4 mg/kg, i.p...
  17. Madani S, Cortes O, Thomas R. Cyproheptadine Use in Children With Functional Gastrointestinal Disorders. J Pediatr Gastroenterol Nutr. 2016;62:409-13 pubmed publisher
    The objective of this study was to evaluate clinical improvement and safety with use of cyproheptadine in functional gastrointestinal disorders (FGIDs) in children...
  18. Compalati E, Canonica G. Efficacy and safety of rupatadine for allergic rhino-conjunctivitis: a systematic review of randomized, double-blind, placebo-controlled studies with meta-analysis. Curr Med Res Opin. 2013;29:1539-51 pubmed publisher
    ..This evidence is strengthened when data are pooled in the form of meta-analysis, where accurate and robust effect estimations are derived from a large population. ..
  19. Calka O, Metin A, Dulger H, Erkoc R. Effect of cyproheptadine on serum leptin levels. Adv Ther. 2005;22:424-8 pubmed
    ..It is known to suppress appetite and increase energy expenditure. Cyproheptadine is a piperidine antihistamine that increases appetite through its antiserotonergic effect on 5-HT2 receptors ..
  20. Hove Madsen L, Llach A, Molina C, Prat Vidal C, Farré J, Roura S, et al. The proarrhythmic antihistaminic drug terfenadine increases spontaneous calcium release in human atrial myocytes. Eur J Pharmacol. 2006;553:215-21 pubmed
    ..This experimental model may be suitable to screen for potential arrhythmogenic side-effects of compounds intended for therapeutical use. ..
  21. Basco L, Ringwald P, Le Bras J. Chloroquine-potentiating action of antihistaminics in Plasmodium falciparum in vitro. Ann Trop Med Parasitol. 1991;85:223-8 pubmed
    ..falciparum. Isobologram analysis showed that both cyproheptadine and azatadine exert a marked synergistic action on chloroquine against chloroquine-resistant, but not against ..
  22. Inoue H, Nagata N, Koshihara Y. Profile of capsaicin-induced mouse ear oedema as neurogenic inflammatory model: comparison with arachidonic acid-induced ear oedema. Br J Pharmacol. 1993;110:1614-20 pubmed
    ..6. The oedema induced by neuropeptides was significantly (P<0.05 or P<0.001) inhibited when cyproheptadine (20 mg kg-1, p.o.), a histamine H, and 5-HT antagonist, was administered before injection...
  23. Santamaría E, Estévez J, Riba J, Izquierdo I, Valle M. Population pharmacokinetic modelling of rupatadine solution in 6-11 year olds and optimisation of the experimental design in younger children. PLoS ONE. 2017;12:e0176091 pubmed publisher
    ..A PK study design was optimised in order to prioritise avoidance of discomfort for enrolled 2-5 year olds by taking only four blood samples from each child and minimising the length of hospital stays. ..
  24. Morais M, Rodrigues F, Costa S, Goulart F, Costa F, Melo I, et al. Nicorandil inhibits mechanical allodynia induced by paclitaxel by activating opioidergic and serotonergic mechanisms. Eur J Pharmacol. 2018;824:108-114 pubmed publisher
    ..p.) or cyproheptadine (5 and 10?mg/kg, i.p.), but not by glibenclamide (20 and 40?mg/kg, p.o.)...
  25. Lewis D, Diamond S, Scott D, Jones V. Prophylactic treatment of pediatric migraine. Headache. 2004;44:230-7 pubmed
    ..5 years. Preventive agents included amitriptyline (n = 73), cyproheptadine (n = 30), propranolol (n = 8), valproic acid (n = 3), naproxen (n = 3), nimodipine (n = 3), imipramine (n = 3),..
  26. Liu X, Lin K. [Effect and its mechanism of substance P on contractile activity of isolated antral muscle strips of rat]. Sheng Li Xue Bao. 1994;46:1-7 pubmed
    ..2) This effect of SP could be partially inhibited by hexamethonium (ganglionic blocker), cyproheptadine (blocker of 5-HT2 receptor), diphenhydramine (blocker of H1 receptor), or aminophylline (inhibitor of ..
  27. Calviño M, Szczupak L. Spatial-specific action of serotonin within the leech midbody ganglion. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2008;194:523-31 pubmed publisher
    ..The results further support the view that the effect of serotonin exhibits a spatial specificity that can be relevant to understand its modulatory actions. ..
  28. Ma Z, Zhang G, Jenney C, Krishnamoorthy S, Tao R. Characterization of serotonin-toxicity syndrome (toxidrome) elicited by 5-hydroxy-l-tryptophan in clorgyline-pretreated rats. Eur J Pharmacol. 2008;588:198-206 pubmed publisher
    ..Lastly, antidotal effect of cyproheptadine and (+)-MK-801 was examined. Both drugs blocked hyperthermia and death...
  29. Enguix M, Sanchez L, Villazon M, Brea J, Tristan H, Caruncho H, et al. Differential regulation of rat peripheral 5-HT(2A) and 5-HT(2B) receptor systems: influence of drug treatment. Naunyn Schmiedebergs Arch Pharmacol. 2003;368:79-90 pubmed
    ..p. administration of (+/-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(+/-)DOI, 1 or 2.5 mg/kg], clozapine, cyproheptadine or rauwolscine (10 mg/kg), 48 h after a single i.p. administration of (+/-)DOI (2...
  30. Frølund L, Etholm B, Irander K, Johannessen T, Odkvist L, Ohlander B, et al. A multicentre study of loratadine, clemastine and placebo in patients with perennial allergic rhinitis. Allergy. 1990;45:254-61 pubmed
    ..Loratadine was safe and well tolerated and was significantly less sedative than clemastine; loratadine may therefore possess an advantage in clinical use in the treatment of perennial allergic rhinitis. ..
  31. Telegdy G, Adamik A, Jászberényi M. Involvement of neurotransmitters in the action of apelin-13 on passive avoidance learning in mice. Peptides. 2013;39:171-4 pubmed publisher
    ..a nonselective ?-adrenergic receptor antagonist), propranolol (a ?-adrenergic receptor antagonist), cyproheptadine (a nonselective 5-HT2 serotonergic receptor antagonist), atropine (a nonselective muscarinic acetylcholine ..
  32. Moyanova S, Kortenska L, Kirov R. High-voltage electroencephalogram spindles in rats, aging and 5-HT2 antagonism. Brain Res. 1998;786:55-63 pubmed
    ..p. administration of three 5-HT2 receptor antagonists: ketanserin, ritanserin and cyproheptadine. In young rats, the three drugs increased the alpha power, but did not change the alpha peak-corresponding ..
  33. Rodriguez L, Diaz J, Nurko S. Safety and efficacy of cyproheptadine for treating dyspeptic symptoms in children. J Pediatr. 2013;163:261-7 pubmed publisher
    To present our experience using cyproheptadine, a potent serotonin antagonist used to stimulate appetite, to treat dyspeptic symptoms in children...
  34. Homnick D, Homnick B, Reeves A, Marks J, Pimentel R, Bonnema S. Cyproheptadine is an effective appetite stimulant in cystic fibrosis. Pediatr Pulmonol. 2004;38:129-34 pubmed
    ..We undertook a trial of cyproheptadine hydrochloride (CH) to determine its effectiveness as an appetite stimulant in 18 adults and children with CF...
  35. Rosskamp R, Haverkamp F, von Kalckreuth G. The effect of cyproheptadine on plasma growth hormone (GH) and on somatostatin response to GH-releasing hormone in man. Horm Metab Res. 1990;22:295-7 pubmed
    b>Cyproheptadine (CPH)--a putative serotonin antagonist--is known to inhibit growth hormone (GH) response to various pharmacological stimuli, as well as during sleep...
  36. Ramage A. Examination of the effects of some 5-HT2 receptor antagonists on central sympathetic outflow and blood pressure in anaesthetised cats. Naunyn Schmiedebergs Arch Pharmacol. 1988;338:601-7 pubmed
    ..Cumulative dose response curves were constructed for the 5-HT2 antagonists cinanserin, ritanserin, cyproheptadine, methiothepin, metergoline and ICI 169,369. These antagonists showed differing effects on the above parameters...
  37. Keam S, Plosker G. Rupatadine: a review of its use in the management of allergic disorders. Drugs. 2007;67:457-74 pubmed
    ..Thus, the introduction of rupatadine extends the range of oral agents available for the treatment of allergic disorders, including allergic rhinitis and CIU. ..
  38. Benneh C, Biney R, Mante P, Tandoh A, Adongo D, Woode E. Maerua angolensis stem bark extract reverses anxiety and related behaviours in zebrafish-Involvement of GABAergic and 5-HT systems. J Ethnopharmacol. 2017;207:129-145 pubmed publisher
    ..The anxiolytic effect was further investigated after pretreatment with flumazenil, granisetron, cyproheptadine, methysergide and pizotifen. M...
  39. Kumar V, Sehgal R. Calotropis procera latex-induced inflammatory hyperalgesia - effect of bradyzide and morphine. Auton Autacoid Pharmacol. 2007;27:143-9 pubmed
    ..effect of bradyzide and morphine on oedema formation and hyperalgesic response was compared with that of cyproheptadine (CPH), a potent inhibitor of DL-induced oedema formation...
  40. Telegdy G, Schally A. Neurotransmitter-mediated action of an antagonist of growth hormone-releasing hormone on anxiolysis in mice. Behav Brain Res. 2012;233:232-6 pubmed publisher
    ..serotonergic receptor antagonist, methysergide, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, and a ?-aminobutyric acid subunit (GABA-A) receptor antagonist, bicuculline...
  41. Fantin S, Maspero J, Bisbal C, Agache I, Donado E, Borja J, et al. A 12-week placebo-controlled study of rupatadine 10 mg once daily compared with cetirizine 10 mg once daily, in the treatment of persistent allergic rhinitis. Allergy. 2008;63:924-31 pubmed publisher
    ..Study treatments were well tolerated. Rupatadine significantly relieves symptoms of PER, providing a rapid onset of action and maintains its effects over a long period of 12-weeks. ..
  42. Barbanoj M, García Gea C, Antonijoan R, Izquierdo I, Donado E, Pérez I, et al. Evaluation of the cognitive, psychomotor and pharmacokinetic profiles of rupatadine, hydroxyzine and cetirizine, in combination with alcohol, in healthy volunteers. Hum Psychopharmacol. 2006;21:13-26 pubmed
    ..Higher doses of rupatadine, in combination with alcohol, may induce cognitive and psychomotor deterioration as hydroxyzine and cetirizine at therapeutic doses. ..
  43. Prelusky D, Rotter B, Thompson B, Trenholm H. Effect of the appetite stimulant cyproheptadine on deoxynivalenol-induced reductions in feed consumption and weight gain in the mouse. J Environ Sci Health B. 1997;32:429-48 pubmed
    ..In this study the efficiency of cyproheptadine (CYP), a serotonin antagonist and known appetite stimulant, to attenuate the adverse effect of DON was ..
  44. Wermuth C. Similarity in drugs: reflections on analogue design. Drug Discov Today. 2006;11:348-54 pubmed
  45. Gaillard A, Gruisen A, De Jong R. The influence of antihistamines on human performance. Eur J Clin Pharmacol. 1988;35:249-53 pubmed
    ..At the conclusion of both experiments, sleepiness was reported by more subjects when treated with clemastine than when treated with loratadine, terfenadine, or placebo. ..
  46. Nance P. Alpha adrenergic and serotonergic agents in the treatment of spastic hypertonia. Phys Med Rehabil Clin N Am. 2001;12:889-905 pubmed
    ..6. Initiate therapy with a low dosage, and titrate judiciously. 7. Stop the titration when functional goal is achieved. 8. If goal is not achieved or if side effects are intolerable, consider a second medication. ..
  47. García Gea C, Ballester M, Martinez J, Antonijoan R, Donado E, Izquierdo I, et al. Rupatadine does not potentiate the CNS depressant effects of lorazepam: randomized, double-blind, crossover, repeated dose, placebo-controlled study. Br J Clin Pharmacol. 2010;69:663-74 pubmed publisher
    ..All treatments were well tolerated. Repeated doses of rupatadine (10 mg orally) did not enhance the CNS depressant effects of lorazepam (2 mg orally, single dose) either in objective psychomotor tasks or in subjective evaluations. ..
  48. Valero A, de la Torre F, Castillo J, Rivas P, Del Cuvillo A, Antepara I, et al. Safety of rupatadine administered over a period of 1 year in the treatment of persistent allergic rhinitis: a multicentre, open-label study in Spain. Drug Saf. 2009;32:33-42 pubmed publisher
    ..This study confirmed the good long-term safety and tolerability of rupatadine at the therapeutic dose of 10 mg/day in patients with PER. ..
  49. Valero A, Izquierdo I, Giralt J, Bartra J, Del Cuvillo A, Mullol J. Rupatadine improves nasal symptoms, quality of life (ESPRINT-15) and severity in a subanalysis of a cohort of Spanish allergic rhinitis patients. J Investig Allergol Clin Immunol. 2011;21:229-35 pubmed
    ..0 [1.2] vs 1.0 [0.9], P < .001) and significantly reduced AR severity (P < .0001). In addition to an improvement in nasal symptoms and HRQoL, rupatadine reduced AR severity after 4 weeks of treatment. ..
  50. McDaniel W. Serotonin syndrome: early management with cyproheptadine. Ann Pharmacother. 2001;35:870-3 pubmed
    ..syndrome after a medication overdose and whose marked mydriasis was quickly reversed by administration of cyproheptadine. This phenomenon was confirmed when other cases of serotonin syndrome were studied...
  51. Izquierdo I, Merlos M, García Rafanell J. Rupatadine: a new selective histamine H1 receptor and platelet-activating factor (PAF) antagonist. A review of pharmacological profile and clinical management of allergic rhinitis. Drugs Today (Barc). 2003;39:451-68 pubmed
    ..Newly published data on its efficacy and safety suggest that this compound may improve the nasal and non-nasal symptoms in comparison to other currently available second generation H1 receptor antihistamines. ..
  52. Frassetto S, Della Santa Rubio A, Lopes J, Pereira P, Brum C, Khazzaka M, et al. Locomotor and peripheral effects of sibutramine modulated by 5-HT2 receptors. Can J Physiol Pharmacol. 2006;84:1239-44 pubmed
    ..On the other hand, cyproheptadine antagonizes serotonin 5-HT(2A), 5-HT(2B), and 5-HT(2C), histamine H1, and muscarinic (M) receptors...
  53. Palotai M, Telegdy G. Anxiolytic effect of the GPR103 receptor agonist peptide P550 (homolog of neuropeptide 26RFa) in mice. Involvement of neurotransmitters. Peptides. 2016;82:20-25 pubmed publisher
    ..subunit A (GABAA) receptor antagonist, bicuculline, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a D2, D3, D4 dopamine receptor antagonist,..