Effect of the putative 5-HT1A antagonists WAY100135 and SDZ 216-525 on 5-HT neuronal firing in the guinea-pig dorsal raphe nucleus.
The selective 5-hydroxytryptamine1A (5-HT1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT, 0.5-35 micrograms kg-1 i.v.) produces a dose related reversible inhibition (ED50 = 6.5 micrograms kg-1 i.v.) of the firing of serotonergic neurones in the dorsal raphe nucleus of the guinea-pig. Administration of N-tert-butyl-3- (4-(2-methoxyphenyl)piperazine-1-yl)-2phenylpropanamide dihydrochloride (WAY100135, 0.5 mg kg-1 i.v.), a specific 5-HT1A antagonist, antagonized the 8-OHDPAT induced inhibition of neuronal firing whilst methyl 4-(4-[4-(1,1,3-trioxo-2H-1,2-benzoisothiazol-2-yl)butyl]-1- piperazinyl) 1 H-indole-2-carboxylate (SDZ 216-525, 0.1-0.5 mg kg-1 i.v.) (also a putative 5-HT1A antagonist) reduced the basal firing of 5-HT neurones and furthermore failed to antagonize the inhibition produced by 8-OHDPAT. These results indicate that WAY 100135 is a silent and selective 5-HT1A antagonist whereas SDZ 216-525 demonstrates a partial agonist activity at the somatodendritic 5-HT1A autoreceptor in the guinea-pig DRN.
Mundey
M K
MK
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, U.K.
Fletcher
A
A
Marsden
C A
CA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*
D007211:Indoles; D010879:Piperazines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013844:Thiazoles; C081293:WAY 100135; C080378:SDZ 216-525; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin