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-HT1A 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 × 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 pIC50 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 A2 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 A2 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 α1-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-HT1A receptor antagonists in in vivo studies.
Document Type: Research Article
Affiliations: Neuropharmacology Research Group, School of Pharmacy and Biomedical Sciences
Publication date: July 1, 2005