A novel probe for the cannabinoid receptor.
The 1,1-dimethylheptyl (DMH) homologue of 7-hydroxy-delta 6-tetrahydrocannabinol (3) is the most potent cannabimimetic substance reported so far. Hydrogenation of 3 leads to a mixture of the epimers of 5'-(1,1-dimethylheptyl)-7-hydroxyhexahydrocannabinol or to either the equatorial (7) or to the axial epimer (8), depending on the catalysts and conditions used. Compound 7 discriminates for delta 1-THC (2) in pigeons (ED50 = 0.002 mg/kg, after 4.5 h), at the potency level of 3, and binds to the cannabinoid receptor with a KD of 45 pM, considerably lower than the Ki of 180 pM measured for compound 3 and the Ki of 2.0 nM measured for CP-55940 (1), a widely employed ligand. Tritiated 7 was used as a novel probe for the cannabinoid receptor.
Devane
W A
WA
Department of Natural Products, Hebrew University, Medical Faculty, Jerusalem, Israel.
Breuer
A
A
Sheskin
T
T
Järbe
T U
TU
Eisen
M S
MS
Mechoulam
R
R
D000818:Animals; D001921:Brain / Q000378:metabolism; D010856:Columbidae; D004193:Discrimination Learning; D004192:Discrimination, Psychological; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008968:Molecular Conformation; D015394:Molecular Structure; D051381:Rats; D011919:Rats, Inbred Strains; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism; D014316:Tritium
D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D014316:Tritium; D013759:Dronabinol; C062018:HU 211