Abstract
A potent 5-hydroxytryptamine (5-HT) 2A receptor inverse agonist and antagonist, ACP-103 [ N-(4-fluorophenylmethyl)- N-(1-methylpiperidin-4-yl)- N′-(4-(2-methylpropyloxy)phenylmethyl) carbamide (2 R,3 R)-dihydroxybutanedioate (2:1, active:salt)], was evaluated for its ability to reduce the primary motor symptom of tremor using tacrine-induced tremulous jaw movements in rats, which is an animal model of parkinsonian tremor. Furthermore, ACP-103 was evaluated for its ability to reduce levodopa-induced dyskinesias in monkeys rendered parkinsonian with MPTP [1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine]. ACP-103 reduced tacrine-induced tremulous jaw movements in rats. In addition, ACP-103 administered in combination with levodopa caused a dose-related reduction in dyskinesias in monkeys. These data suggest that ACP-103 may have the potential to reduce tremor and levodopa-induced dyskinesias in Parkinson's disease.
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