Sigma receptor binding affinity and inhibition of apomorphine-induced climbing.
Several relatively selective compounds with affinity for the sigma binding site were assessed for their ability to inhibit apomorphine-induced climbing in the mouse. Although, the majority of compounds inhibited apomorphine-induced climbing, there was no correlation between the ability to inhibit climbing and potency in sigma binding assays using [3H]1,3-di-o-tolylguanidine (DTG) or [3H](+)-pentazocine as ligands. The potency of the compounds to inhibit binding to muscarinic M1 or M2 receptors correlated with the potency to inhibit apomorphine-induced climbing. However, several of the compounds that inhibit climbing had microM affinity at muscarinic receptors. Whether these concentrations were achieved in vivo is unclear. Our data suggest that sigma activity per se is not responsible for inhibition of apomorphine-induced climbing.
Department of Neuroscience, Sterling-Winthrop Pharmaceutical Research Division, Rensselaer, NY 12144.
P M
PM
Fritz
D L
DL
DeHaven-Hudkins
L C
LC
Fleissner
F Y
FY
Ford-Rice
D
D
Luttinger
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000378:metabolism; D008297:Male; D051379:Mice; D010423:Pentazocine / Q000378:metabolism; D011869:Radioligand Assay; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000378:metabolism*
D006146:Guanidines; D017480:Receptors, sigma; C050232:1,3-ditolylguanidine; D001058:Apomorphine; D010423:Pentazocine