The authors examined the effect of Δ1 tetrahydrocannabinol (Δ1 THC) and 12 of its derivatives on the uptake of 3H labeled norepinephrine (NE), dopamine (DA), serotonin (5HT) and γ aminobutyric acid (GABA) into synaptosomes in homogenates of various regions of rat brain. Δ1 THC inhibits the accumulation of NE and 5 HT into hypothalamic preparations and DA into the corpus striatum with K(i) values of about 12 to 25 μM while GABA uptake into cerebral cortical preparations is inhibited less (K(i) = 140 μM). The affinities of Δ6 THC, 7 hydroxy Δ1 THC, 7 hydroxy Δ6 THC and cannabidiol for 5 HT, NE and GABA transports are similar to values for Δ1 THC, while cannabigerol, cannabinol and Δ6 THC 7 oic acid have substantially less affinity. Thus, hydroxylation of C 7 in Δ6 THC does not alter inhibitory potency, but its oxidation to an acid and aromatization of ring A greatly reduce affinity. The hydroxyl at C 31 of ring C is critical for inhibition of NE, 5 HT and GABA uptake, since its acetylation of methylation abolishes activity. Inhibition of NE, DA, 5 HT and GABA uptake by all cannabinoids examined is noncompetitive. Only about 1% of Δ1 THC and Δ6 THC and 5% of cannabidiol are fully soluble under our experimental conditions.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Dec 1 1975|
ASJC Scopus subject areas
- Molecular Medicine