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Abstract

Cannabinoids: influence on neurotransmitter uptake in rat brain synaptosomes.

S P Banerjee, S H Snyder and R Mechoulam
Journal of Pharmacology and Experimental Therapeutics July 1975, 194 (1) 74-81;
S P Banerjee
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S H Snyder
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R Mechoulam
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Abstract

We have examined the effect of Delta1-tetrahydrocannabinol (delat1-THC) and 12 of its derivatives on the uptake of 3H-labeled norepinephrine (NE), dopamine (DA), serotonin (5-HT) gamma-aminobutyric acid (GABA) into synaptosomes in homogenates of various regions of rat brain. Delta1-THC inhibits the accumulation of NE and 5-HT into hypothalamic preparations and DA into the corpus striatum with Ki values of about 12 to 25 muM while GABA uptake into cerebral cortical preparations is inhibited less (Ki = 140 muM). The affinities of delta6-THC, 7-hydroxy-delta1-THC, 7-hydroxy-delta6-THC and cannabidiol for 5-HT, NE and GABA transports are similar to values for delta1-THC, while cannabigerol, cannabinol and delta6-THC-7-oic acid have substantially less affinity. Thus, hydroxylation of C-7 in delta6-THC does not alter inhibitory potency, but its oxidation to an acid and aromatization of ring A greatly reduce affinity. The hydroxyl at C-3(1) of ring C is critical for inhibition of NE, 5-HT and GABA uptake, since its acetylation or methylation abolishes activity. Inhibition of NE, DA, 5-HT and GABA uptake by all cannabinoids examined is noncompetitive. Only about 1% of delta1-THC and delta6-THC and 5% of cannabidiol are fully soluble under our experimental conditions.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 194, Issue 1
1 Jul 1975
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Abstract

Cannabinoids: influence on neurotransmitter uptake in rat brain synaptosomes.

S P Banerjee, S H Snyder and R Mechoulam
Journal of Pharmacology and Experimental Therapeutics July 1, 1975, 194 (1) 74-81;

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Abstract

Cannabinoids: influence on neurotransmitter uptake in rat brain synaptosomes.

S P Banerjee, S H Snyder and R Mechoulam
Journal of Pharmacology and Experimental Therapeutics July 1, 1975, 194 (1) 74-81;
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