Competitive inhibition of delta8-tetrahydrocannabinol and its active metabolites for cannabinoid receptor binding.
In vitro binding characteristics of delta8-tetrahydrocannabinol (delta8-THC) and its metabolites, 11-hydroxy-delta8-THC (11-OH-delta8-THC) and 11-oxo-delta8-THC, as well as an inactive metabolite, delta8-THC-11-oic acid, as a cannabinoid receptor site from bovine cortex were examined using the specific agonist [3H]CP-55940. 11-OH-delta8-THC and 11-oxo-delta8-THC strongly inhibited the specific binding of [3H]CP-55940. The Ki values of 11-OH-delta8-THC and 11-oxo-delta8-THC for the specific binding of [3H]CP-55940 were 52 and 143 nM, respectively, whereas that of delta8-THC-11-oic acid was 917 nM. Scatchard plot analyses indicated that 11-OH-delta8-THC and 11-oxo-delta8-THC caused a significant increase in the apparent KD value without changing the apparent Bmax. These results reveal that active metabolites of delta8-THC also competitively bind to the cannabinoid receptor as agonists.
Yamamoto
I
I
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Kimura
T
T
Kamei
A
A
Yoshida
H
H
Watanabe
K
K
Ho
I K
IK
Yoshimura
H
H
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D013759:Dronabinol / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D006213:Hallucinogens / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D010084:Oxidation-Reduction; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism
D006213:Hallucinogens; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D013759:Dronabinol