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

Ibogaine and 18‐methoxycoronaridine are naturally occurring alkaloids reported to possess antiaddictive properties in several models of drug dependence. We have examined their effect at μ‐opioid receptors regulating neurogenic contractions of several smooth muscle preparations and also against spontaneous contractions of the rat isolated portal vein. Ibogaine (pIC50 5.28) and 18‐methoxycoronaridine (pIC50 5.05) caused a concentration‐dependent inhibition of cholinergic contractions of the guinea‐pig ileum which was not affected by the opioid receptor antagonist naloxone (1 μM). In the rat isolated vas deferens ibogaine and 18‐methoxycoronaridine caused a concentration‐dependent enhancement of purinergic contractions. Both agents (30 μM) caused a 3–5 fold rightward displacement of DAMGO‐induced inhibition of purinergic contractions, but similar effects were observed for ibogaine against α2‐adrenoceptor‐mediated inhibition of neurogenic responses. In the guinea‐pig isolated bladder both ibogaine (10 μM) and 18‐methoxycoronaridine (10 μM) caused a 2 fold increase in the purinergic component of neurogenic contractions without significantly altering cholinergic contractions or responses to exogenous ATP. In contrast, ibogaine (1–30 μM), but not 18‐methoxycoronaridine, caused a concentration‐dependent enhancement of spontaneous contractions of the rat isolated portal vein. In summary, while ibogaine and 18‐methoxycoronaridine modulated electrically‐evoked contractions in the three preparations examined, we have no evidence for a selective interaction with pre‐junctional μ‐opioid receptors. The pronounced enhancement of purinergic contractions produced by both agents is a novel finding and worthy of further investigation. British Journal of Pharmacology (2000) 129, 1561–1568; doi:10.1038/sj.bjp.0703227