ABSTRACT
3H-delta 9-Tetrahydrocannabinol (3H-delta 9-THC), 3H-cannabidiol (3H-CBD) and 3H-cannabinol (3H-CBN) were administered (1 mg/kg) to male rats which were decapitated either 0.5, 1, 15, 30 or 90 min later. The plasma concentration was similar for all cannabinoids throughout the time course. After 5 min greater than 80% of the plasma radioactivity in each treatment was due to metabolites. Radioactivity rapidly entered brain after the administration of 3H-CBD, 3H-CBN, and 3H-delta 9-THC. The concentrations of unchanged 3H-CBD aand 3H-CBN in whole brain were higher than that of 3H-delta 9-THC 5 min after administration. Regional distribution of radioactivity in the brain after 5 min was similar for all three cannabinoids, the only significant difference being in hypothalamus. Coadministration of 3H-delta 9-THC with a five-fold excess of either CBD or delta 9-THC did not produce any significant alteration in the levels of radioactivity in brain or plasma 5 min after their injection. The difference in behavioral activity of delta 9-THC, CBD and CBN cannot be explained by penetrability or regional distribution in the brain.
Subject(s)
Brain/metabolism , Cannabidiol/metabolism , Cannabinoids/metabolism , Cannabinol/metabolism , Dronabinol/metabolism , Animals , Drug Interactions , Kinetics , Male , Rats , Time FactorsSubject(s)
Solanine/analogs & derivatives , Animals , Cricetinae , Feces/analysis , Mesocricetus , Solanine/metabolism , Time FactorsABSTRACT
Liver mitochondria from alphatocopherol deficient rats swell more rapidly, both spontaneously and in the presence of GSH, than those from control animals. The increased swelling of deficient mitochondria induced by GSH was completely eliminated when mitochondria were left longer than two hours at 0 degrees in the suspending medium. GSH-induced swelling of liver mitochondria from alpha-tocopherol deficient rats is reversed by ATP, polyvinyl pyrrolidone (PVP) and by oral administration alpha-tocopherol (2 mg/day per rat). Swelling of mitochondria in the above system was completely inhibited by the respiratory chain inhibitor, cyanide (.001 M), and partially by azide (0.001 M). We suggest that the swelling tendency of liver mitochondria from alpha-tocopherol deficient rats might be associated with an altered respiratory mechanism and/or an alteration in membrane permeability.
