A 5-HT2A receptor inverse agonist, ACP-103, reduces tremor in a rat model and levodopa-induced dyskinesias in a monkey model.

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 (2R,3R)-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.

• Authors: Kimberly E Vanover, Adrienne J Betz, Suzanne M Weber, Francesco Bibbiani, Aiste Kielaite, David M Weiner, Robert E Davis, Thomas N Chase, John D Salamone
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 90 Issue 4 Pg. 540-4 (Oct 2008) ISSN: 0091-3057 [Print] United States
• PMID: 18534670 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Dopamine Agents
• Piperidines
• Serotonin 5-HT2 Receptor Agonists
• Serotonin Receptor Agonists
• Levodopa
• Urea
• pimavanserin

Topics

• Animals
• Data Interpretation, Statistical
• Dopamine Agents
• Dyskinesia, Drug-Induced (drug therapy)
• Jaw (physiology)
• Levodopa
• MPTP Poisoning (drug therapy)
• Macaca fascicularis
• Male
• Piperidines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Serotonin 5-HT2 Receptor Agonists
• Serotonin Receptor Agonists (pharmacology)
• Tremor (drug therapy)
• Urea (analogs & derivatives, pharmacology)