The novel selective and silent 5-HT1A receptor antagonist (+)-WAY-100135 aggravates dystonic movements in a mutant hamster model. 1994

W Löscher, and A Richter
Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Hannover, Germany.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008647 Mesocricetus A genus in the order Rodentia and family Cricetidae. One species, Mesocricetus auratus or golden hamster is widely used in biomedical research. Hamsters, Golden,Hamsters, Golden Syrian,Hamsters, Syrian,Mesocricetus auratus,Syrian Golden Hamster,Syrian Hamster,Golden Hamster,Golden Hamster, Syrian,Golden Hamsters,Golden Syrian Hamsters,Hamster, Golden,Hamster, Syrian,Hamster, Syrian Golden,Syrian Hamsters
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D004421 Dystonia An attitude or posture due to the co-contraction of agonists and antagonist muscles in one region of the body. It most often affects the large axial muscles of the trunk and limb girdles. Conditions which feature persistent or recurrent episodes of dystonia as a primary manifestation of disease are referred to as DYSTONIC DISORDERS. (Adams et al., Principles of Neurology, 6th ed, p77) Muscle Dystonia,Dystonia, Diurnal,Dystonia, Limb,Dystonia, Paroxysmal,Diurnal Dystonia,Dystonia, Muscle,Limb Dystonia,Paroxysmal Dystonia
D005260 Female Females
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors
D012702 Serotonin Antagonists Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS. 5-HT Antagonist,5-HT Antagonists,5-Hydroxytryptamine Antagonist,5-Hydroxytryptamine Antagonists,Antiserotonergic Agent,Antiserotonergic Agents,Serotonin Antagonist,Serotonin Blockader,Serotonin Blockaders,Serotonin Receptor Antagonist,Serotonin Receptor Blocker,Antagonists, 5-HT,Antagonists, 5-Hydroxytryptamine,Antagonists, Serotonin,Serotonin Receptor Antagonists,Serotonin Receptor Blockers,5 HT Antagonist,5 HT Antagonists,5 Hydroxytryptamine Antagonist,5 Hydroxytryptamine Antagonists,Agent, Antiserotonergic,Agents, Antiserotonergic,Antagonist, 5-HT,Antagonist, 5-Hydroxytryptamine,Antagonist, Serotonin,Antagonist, Serotonin Receptor,Antagonists, 5 HT,Antagonists, 5 Hydroxytryptamine,Antagonists, Serotonin Receptor,Blockader, Serotonin,Blockaders, Serotonin,Blocker, Serotonin Receptor,Blockers, Serotonin Receptor,Receptor Antagonist, Serotonin,Receptor Antagonists, Serotonin,Receptor Blocker, Serotonin,Receptor Blockers, Serotonin

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