The effect of chronic administration of sarizotan, 5-HT1A agonist/D3/D4 ligand, on haloperidol-induced repetitive jaw movements in rat model of tardive dyskinesia.
Dyskinesia is the most troublesome side effect in long-term treatment of both Parkinson's disease (PD) and schizophrenia. The 5-HT1A agonist and D3/D4 ligand sarizotan [Bartoszyk, G.D., van Amsterdam, C., Greiner, H.E., Rautenberg, W., Russ, H., Seyfried, C.A., 2004. Sarizotan, a serotonin 5-HT1A receptor agonist and dopamine receptor ligand. 1. Neurochemical profile. J. Neural Transm. 111, 113-126.] is in clinical development for the treatment of PD-associated dyskinesia. Because 5-HT1A agonists are known to counteract antipsychotic-induced motor side effects, sarizotan was investigated for its effects in two rat models of tardive dyskinesia (TD). The acute administration of sarizotan (0.17-13.5 mg/kg i.p.) reduced episodes of SKF 38393-induced repetitive jaw movements (RJM) in rats with a maximal effect at 1.5 mg/kg. In a chronic study, sarizotan (0.04-9 mg/kg/day), administered in the drinking water for 7 weeks during withdrawal from chronic haloperidol treatment (1.5 mg/kg/day), dose-dependently reversed haloperidol-induced RJM, significant at the doses of 1.5 and 9 mg/kg. Agonism at 5-HT1A receptors may be mediating the inhibitory effect of sarizotan on RJM in rat models of tardive dyskinesia.
Rosengarten
Helen
H
Department of Psychiatry, Millhauser Laboratories, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Bartoszyk
Gerd D
GD
Quartermain
David
D
Lin
Yan
Y
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000633:toxicity; D018492:Dopamine Antagonists / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000209:etiology; D006220:Haloperidol / Q000633:toxicity; D007568:Jaw / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009068:Movement / Q000187:drug effects*; D009930:Organic Chemicals / Q000008:administration & dosage; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage*; D013997:Time Factors
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D009930:Organic Chemicals; D017366:Serotonin Receptor Agonists; C443959:sarizotan; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D006220:Haloperidol