The effects of (+/-)-idazoxan and its stereoisomers on mouse vas deferens motility in vitro. A comparison with yohimbine.
The effects of idazoxan (IDZ) and its stereoisomers were compared to that of a classical alpha 2-antagonist, yohimbine (YOH), on para-aminoclonidine (PAC)- and norepinephrine (NE)-mediated inhibition of the twitch response evoked in the mouse vas deferens by low-frequency (0.1 Hz) field stimulation. (+/-)-IDZ and (+)-IDZ antagonized the inhibitory effects of PAC, (+)-IDZ being twice as potent as (+/-)-IDZ; in contrast, antagonism by (-)-IDZ failed to meet Schild criteria for a competitive mechanism. YOH completely reversed the inhibition of twitch response induced by NE, but not that induced by PAC; in the latter case, residual inhibition was almost fully reversed by (+)-IDZ and to a lesser extent by (+/-)-IDZ, while (-)-IDZ proved ineffective. These results provide pharmacological evidence of alpha 2-receptor heterogeneity at the vas deferens level. A possible additional mechanism involving imidazoline binding sites is discussed.
Carratù
M R
MR
Institute of Pharmacology, University of Bari, School of Medicine, Italy.
Navarra
P
P
De Serio
A
A
Serio
M
M
Preziosi
P
P
Mitolo-Chieppa
D
D
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology*; D019329:Idazoxan; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000494:pharmacology; D013237:Stereoisomerism; D014649:Vas Deferens / Q000187:drug effects* / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D015016:Yohimbine; D003000:Clonidine; D009638:Norepinephrine; D019329:Idazoxan