A comparison of the effects of the 5HT1A antagonists MM-77 and WAY-100635 on the mouse isolated vasa deferentia.
1. Experiments were carried out to characterize the possible adrenergic properties of the 5-HT(1A) antagonists WAY 100635 and MM-77 using the mouse isolated vasa deferentia preparation. 2. When vasa deferentia were preincubated for 10 min in the presence of MM-77 (10(-8)-10(-6) m) or WAY100635 (10(-8)-7 x 10(-7) m), a concentration-dependent inhibition of the contractile response to submaximal electrical field stimulation (10 Hz, 50 V, 50 ms) was observed with pIC(50) values of 7.05 +/- 0.01 and 6.85 +/- 0.1 respectively. 3. MM-77 (10(-8)-10(-6) m) antagonized the contractile responses of the vasa deferentia to phenylephrine (PE) (10(-6)-10(-3) m) in a concentration-dependent manner. Schild plots of these data were linear and yielded a mean rhoA(2) value of 6.81 +/- 0.084. The mean slope was 1.42 +/- 0.22. 4. WAY100635 (10(-8)-10(-6) m) antagonized the contractile responses of the vasa deferentia to PE (10(-6)-10(-3) m) in a concentration-dependent manner. Schild plots of these data were linear and yielded a mean rhoA(2) value of 7.05 +/- 0.08. The mean slope was 0.97 +/- 0.1. 5. The results suggest that while WAY100635 acts as a competitive antagonist at alpha(1)-adrenoceptors, MM-77 displays non-competitive antagonist characteristics at this receptor subtype. 6. These results may have important implications for the use of these compounds as 5-HT(1A) receptor antagonists in in vivo studies.
Arkle
M J
MJ
Neuropharmacology Research Group, School of Pharmacy and Biomedical Sciences, University of Portsmouth, PO1 2DT, UK.
Arkle
S
S
Ebenezer
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IS
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013388:Succinimides / Q000494:pharmacology*; D014649:Vas Deferens / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
C413583:MM 77; D010879:Piperazines; D011725:Pyridines; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D013388:Succinimides; D014662:Vasoconstrictor Agents; D044282:Receptor, Serotonin, 5-HT1A; D010656:Phenylephrine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide