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.

Abstract

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.

• Authors: Helen Rosengarten, Gerd D Bartoszyk, David Quartermain, Yan Lin
• Journal: Progress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 30 Issue 2 Pg. 273-9 (Mar 2006) ISSN: 0278-5846 [Print] England
• PMID: 16229932 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dopamine Agonists
• Dopamine Antagonists
• Organic Chemicals
• Serotonin Receptor Agonists
• sarizotan
• 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
• Haloperidol

Topics

• 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (toxicity)
• Analysis of Variance
• Animals
• Behavior, Animal (drug effects)
• Disease Models, Animal
• Dopamine Agonists (toxicity)
• Dopamine Antagonists (toxicity)
• Dose-Response Relationship, Drug
• Drinking Behavior (drug effects)
• Drug Administration Schedule
• Drug Interactions
• Dyskinesia, Drug-Induced (drug therapy, etiology)
• Haloperidol (toxicity)
• Jaw (drug effects, physiopathology)
• Male
• Motor Activity (drug effects)
• Movement (drug effects)
• Organic Chemicals (administration & dosage)
• Psychomotor Performance (drug effects)
• Rats
• Rats, Sprague-Dawley
• Serotonin Receptor Agonists (administration & dosage)
• Time Factors