The novel selective and silent 5-HT1A receptor antagonist (+)-WAY-100135 aggravates dystonic movements in a mutant hamster model.

Abstract

Several clinical and experimental findings suggest that abnormal serotonin (5-HT) function may be involved in movement disorders such as dystonia, and it was proposed that selective 5-HT1A receptor antagonists may be of benefit in treating such disorders. In the present study, the novel, highly selective and silent 5-HT1A receptor antagonist (+)-WAY-100135 (N-tert-butyl-3(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylprop ionamide) was tested in an inbred line of Syrian hamsters with generalized dystonia, i.e. a frequent movement disorder in humans. In order to demonstrate that WAY-100135 acts as a 5-HT1A receptor antagonist in the hamster, the drug was shown to antagonize the behavioural syndrome induced by 8-hydroxy-2-(di-n-propylamino)tetralin. When administered at 5-HT1A receptor antagonistic doses in dystonic hamsters, (+)-WAY-100135 dramatically aggravated the dystonic attacks. The data thus suggest that, in contrast to previous theoretical proposals, 5-HT1A receptor antagonists provide no novel therapeutic approach to involuntary movement disorders such as dystonia.

• Authors: W Löscher, A Richter
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 255 Issue 1-3 Pg. 235-8 (Apr 01 1994) ISSN: 0014-2999 [Print] Netherlands
• PMID: 8026548 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Piperazines
• Serotonin Antagonists
• WAY 100135
• 8-Hydroxy-2-(di-n-propylamino)tetralin

Topics

• 8-Hydroxy-2-(di-n-propylamino)tetralin (antagonists & inhibitors, pharmacology)
• Animals
• Behavior, Animal (drug effects)
• Cricetinae
• Dystonia (physiopathology)
• Female
• Male
• Mesocricetus
• Mutation
• Piperazines (pharmacology)
• Serotonin Antagonists