Evaluation of the interactions of serotonergic and adrenergic drugs with mu, delta, and kappa opioid binding sites.
Several serotonergic and adrenergic agents were tested for an ability to interact with mu, delta, and kappa opioid binding sites. Spiroxatrine interacted nearly equipotently with all three opioid subtypes, yielding Ki values near 110 nM. A number of other serotonergic and adrenergic agents interacted with affinities in the 1-50 microM range. Most of the other compounds tested in this study were found to compete for opioid binding to some degree, though not achieving a 50% inhibition of binding at concentrations up to 100 microM. If this interaction between monoaminergic agents and opioid receptors is found to have functional significance, it must be considered in the interpretation of results from studies using these agents to evaluate the contribution of monoaminergic systems to opioid-mediated events.
NovaScreen Division, Nova Pharmaceutical Corporation, Baltimore, MD.
P J
PJ
Monroe
S E
SE
Perschke
T
T
Crisp
D J
DJ
Smith
D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D016548:Prosencephalon / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D012701:Serotonin / Q000502:physiology*; D013566:Sympathomimetics / Q000494:pharmacology*
D015259:Dopamine Agents; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013566:Sympathomimetics; D012701:Serotonin