WAY-100635 and GR127935: effects on 5-hydroxytryptamine-containing neurones.
N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2- pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY-100635) is a potent and selective 5-HT1A receptor antagonist in a slice preparation of the guinea pig dorsal raphe nucleus: the inhibitory actions on 5-HT neuronal firing of 5-hydroxytryptamine (5-HT, serotonin), 5-carboxamidotryptamine (5-CT) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), but not those of baclofen, were abolished by 30 nM WAY-100635. The selective 5-HT1D receptor antagonist N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'- methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl) [1,1-biphenyl]-4-carboxamide (GR127935, 300 nM) did not attenuate the 5-HT induced inhibition, indicating that 5-HT1D receptors do not contribute to the inhibitory action of exogenous 5-HT on 5-HT neurones.
Craven
R
R
University Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford, UK.
Grahame-Smith
D
D
Newberry
N
N
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*
D010069:Oxadiazoles; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C090701:GR 127935; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide