Description:
The effects of several ligands which interact with the σ‐binding site were studied on the electrically‐evoked (0.1 Hz) neurogenic twitch contractions of the mouse isolated vas deferens.(+)‐3‐(3‐Hydroxyphenyl)‐N‐(1‐propyl)piperidine ((+)‐3‐PPP) (10−8–10−5m), inhibited the neurogenic twitch contractions. This inhibitory action was unaffected by naloxone (10−6m), idazoxan (10−6m), cocaine (10−6m) or tyramine (10−4–3 × 10−4m), but was abolished by the dopamine D2‐antagonist, sulpiride (10−6m). Therefore, in order to study the potentiating actions of σ ligands, sulpiride (10−6m) was used to prevent any inhibitory actions mediated via dopamine D2‐receptors.In the presence of sulpiride (10−6m), haloperidol (10−6–10−5m), (+)‐3‐PPP (10−6−3 × 10−4m) and (+)‐N‐allyl‐N‐normetazocine ((+)‐SKF 10,047) (10−5–10−4m) each reversibly potentiated the neurogenic twitch contractions in a concentration‐dependent manner. The rank order of potency was haloperidol > (+)‐3‐PPP > (+)‐SKF 10,047.The stereoisomers of 3‐PPP displayed stereoselectivity with (+)‐3‐PPP being more potent than (−)‐3‐PPP.At a concentration that did not potentiate the twitch contractions, (3 × 10−7m), haloperidol did not antagonize the potentiating action of (+)‐3‐PPP (3 × 10−5m).1,3‐Di‐O‐tolyguanidine (DTG) (10−8–10−5m) had no effect on the amplitude of twitch contractions and did not affect the potentiating action of (+)‐3‐PPP (10−5−3 × 10−5m).It is concluded that σ‐ligands potentiate neurogenic twitch contractions of the mouse isolated vas deferens via a site that is different from the central σ‐binding site.