Ropizine concurrently enhances and inhibits [3H]dextromethorphan binding to different structures of the guinea pig brain: autoradiographic evidence for multiple binding sites.
Ropizine (10 microM) produces a simultaneous enhancement and inhibition of [3H]dextromethorphan (DM) high-affinity binding to different areas of the guinea pig brain. These results imply that there are two distinct types of high-affinity [3H]DM binding sites, which are present in variable proportions in different brain structures. The ropizine-enhanced [3H]DM binding type was preferentially inhibited by (+)-pentazocine. This is consistent with the presumption that the (+)-pentazocine-sensitive site is identical with the common site for DM and 3-(-3-Hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP). The second binding type, which is inhibited by ropizine and is not so sensitive to (+)-pentazocine, has not been fully characterized. This study demonstrates that the biphasic effects of ropizine are due, at least in part, to the effects of ropizine on two different types of [3H]DM binding sites. However, this study does not rule out that common DM/(+)-3-PPP site also might be inhibited by higher concentrations of ropizine.
Canoll
P D
PD
Department of Pharmacology, N. Y. U. Medical Center, NY 10016.
Smith
P R
PR
Musacchio
J M
JM
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001345:Autoradiography; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003915:Dextromethorphan / Q000378:metabolism*; D006168:Guinea Pigs; D007981:Levorphanol / Q000031:analogs & derivatives*; D010423:Pentazocine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*
D000927:Anticonvulsants; D010879:Piperazines; D007981:Levorphanol; D003915:Dextromethorphan; C006249:ropizine; D010423:Pentazocine