Pharmacological comparison of the effect of ibogaine and 18-methoxycoronaridine on isolated smooth muscle from the rat and guinea-pig

1 Ibogaine and 18-methoxycoronaridine are naturally occurring alkaloids rep orted to possess antiaddictive properties in several models of drug depende nce. We have examined their effect at mu-opioid receptors regulating neurog enic contractions of several smooth muscle preparations and also against sp ontaneous contractions of the rat isolated portal vein. 2 Ibogaine (pIC(50) 5.28) and 18-methoxycoronaridine (pIC(50) 5.05) caused a concentration-dependent inhibition of cholinergic contractions of the gui nea-pig ileum which was not affected by the opioid receptor antagonist nalo xone (1 mu M). 3 In the rat isolated vas deferens ibogaine and 18-methoxycoronaridine caus ed a concentration-dependent enhancement of purinergic contractions. Both a gents (30 mu M) caused a 3-5 fold rightward displacement of DAMGO-induced i nhibition of purinergic contractions, but similar effects were observed for ibogaine against alpha(2)-adrenoceptor-mediated inhibition of neurogenic r esponses. 4 In the guinea-pig isolated bladder both ibogaine (10 mu M) and 18-methoxy coronaridine (10 mu M) caused a 2 fold increase in the purinergic component of neurogenic contractions without significantly altering cholinergic cont ractions or responses to exogenous ATP. In contrast, ibogaine (1-30 mu M), but not 18-methoxycoronaridine, caused a concentration-dependent enhancemen t of spontaneous contractions of the rat isolated portal vein. 5 In summary, while ibogaine and 18-methoxycoronaridine modulated electrica lly-evoked contractions in the three preparations examined, we have no evid ence for a selective interaction with pre-junctional mu-opioid receptors. T he pronounced enhancement of purinergic contractions produced by both agent s is a novel finding and worthy of further investigation.