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Metabolic disposition of delta 8-tetrahydrocannabinol and its active metabolites, 11-hydroxy-delta 8-tetrahydrocannabinol and 11-oxo-delta 8-tetrahydrocannabinol, in mice.
Drug Metab Dispos. 1981 May-Jun; 9(3):261-4.DM

Abstract

Metabolic disposition of delta 8-tetrahydrocannabinol (delta 8-THC), 11-hydroxy-delta 8-THC (11-OH-delta 8-THC), and 11-oxo-delta 8-THC was studied in mouse blood, liver, and brain. After administration of these cannabinoids at a dose of 10 mg/kg iv, the concentration in blood declined biphasically. The biological half-lives of the slower phases were 32, 12, and 6 min, respectively, for delta 8-THC, 11-OH-delta 8-THC, and 11-oxo-delta 8-THC. 11-OH- and 11-oxo-delta 8-THC were also eliminated faster from brain than is delta 8-THC. The peak levels of 11-OH- and 11-oxo-delta 8-THC in brain were, however, higher (10.64 and 4.25 microgram/g, respectively) than that of delta 8-THC (3.48 microgram/g) at 0.5 min after the iv injection (10 mg/kg). These results indicate that 11-OH- and 11-oxo-delta 8-THC are distributed more readily from blood to brain in mice than is delta 8-THC, and explain the greater pharmacological activity of these metabolites, as reported previously. It was also interesting to note that a much higher level of 11-OH-delta 8-THC (3.27 microgram/g) was found in brain than in liver(0.74 microgram/g) and blood (0.29 microgram/ml) at 15 min after the injection of 11-oxo-delta 8-THC (10 microgram/kg, iv). In this case the levels of 11-OH-delta 8-THC were always higher than those of 11-oxo-delta 8-THC. The results suggest that 11-OH-delta 8-THC may play an important role in the pharmacological effects of 11-oxo-delta 8-THC. In additional experiments, SKF 525-A (25 mg/kg, ip) inhibited the metabolism of 11-OH-delta 8-THC to 11-oxo-delta 8-THC, supporting the previous suggestion that this oxidation, as well as the 11-hydroxylation of delta 8-THC, is mediated by the microsomal mono-oxygenase system.

Authors

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Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

6113937

Citation

Watanabe, K, et al. "Metabolic Disposition of Delta 8-tetrahydrocannabinol and Its Active Metabolites, 11-hydroxy-delta 8-tetrahydrocannabinol and 11-oxo-delta 8-tetrahydrocannabinol, in Mice." Drug Metabolism and Disposition: the Biological Fate of Chemicals, vol. 9, no. 3, 1981, pp. 261-4.
Watanabe K, Yamamoto I, Oguri K, et al. Metabolic disposition of delta 8-tetrahydrocannabinol and its active metabolites, 11-hydroxy-delta 8-tetrahydrocannabinol and 11-oxo-delta 8-tetrahydrocannabinol, in mice. Drug Metab Dispos. 1981;9(3):261-4.
Watanabe, K., Yamamoto, I., Oguri, K., & Yoshimura, H. (1981). Metabolic disposition of delta 8-tetrahydrocannabinol and its active metabolites, 11-hydroxy-delta 8-tetrahydrocannabinol and 11-oxo-delta 8-tetrahydrocannabinol, in mice. Drug Metabolism and Disposition: the Biological Fate of Chemicals, 9(3), 261-4.
Watanabe K, et al. Metabolic Disposition of Delta 8-tetrahydrocannabinol and Its Active Metabolites, 11-hydroxy-delta 8-tetrahydrocannabinol and 11-oxo-delta 8-tetrahydrocannabinol, in Mice. Drug Metab Dispos. 1981 May-Jun;9(3):261-4. PubMed PMID: 6113937.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metabolic disposition of delta 8-tetrahydrocannabinol and its active metabolites, 11-hydroxy-delta 8-tetrahydrocannabinol and 11-oxo-delta 8-tetrahydrocannabinol, in mice. AU - Watanabe,K, AU - Yamamoto,I, AU - Oguri,K, AU - Yoshimura,H, PY - 1981/5/1/pubmed PY - 1981/5/1/medline PY - 1981/5/1/entrez SP - 261 EP - 4 JF - Drug metabolism and disposition: the biological fate of chemicals JO - Drug Metab Dispos VL - 9 IS - 3 N2 - Metabolic disposition of delta 8-tetrahydrocannabinol (delta 8-THC), 11-hydroxy-delta 8-THC (11-OH-delta 8-THC), and 11-oxo-delta 8-THC was studied in mouse blood, liver, and brain. After administration of these cannabinoids at a dose of 10 mg/kg iv, the concentration in blood declined biphasically. The biological half-lives of the slower phases were 32, 12, and 6 min, respectively, for delta 8-THC, 11-OH-delta 8-THC, and 11-oxo-delta 8-THC. 11-OH- and 11-oxo-delta 8-THC were also eliminated faster from brain than is delta 8-THC. The peak levels of 11-OH- and 11-oxo-delta 8-THC in brain were, however, higher (10.64 and 4.25 microgram/g, respectively) than that of delta 8-THC (3.48 microgram/g) at 0.5 min after the iv injection (10 mg/kg). These results indicate that 11-OH- and 11-oxo-delta 8-THC are distributed more readily from blood to brain in mice than is delta 8-THC, and explain the greater pharmacological activity of these metabolites, as reported previously. It was also interesting to note that a much higher level of 11-OH-delta 8-THC (3.27 microgram/g) was found in brain than in liver(0.74 microgram/g) and blood (0.29 microgram/ml) at 15 min after the injection of 11-oxo-delta 8-THC (10 microgram/kg, iv). In this case the levels of 11-OH-delta 8-THC were always higher than those of 11-oxo-delta 8-THC. The results suggest that 11-OH-delta 8-THC may play an important role in the pharmacological effects of 11-oxo-delta 8-THC. In additional experiments, SKF 525-A (25 mg/kg, ip) inhibited the metabolism of 11-OH-delta 8-THC to 11-oxo-delta 8-THC, supporting the previous suggestion that this oxidation, as well as the 11-hydroxylation of delta 8-THC, is mediated by the microsomal mono-oxygenase system. SN - 0090-9556 UR - https://www.unboundmedicine.com/medline/citation/6113937/Metabolic_disposition_of_delta_8_tetrahydrocannabinol_and_its_active_metabolites_11_hydroxy_delta_8_tetrahydrocannabinol_and_11_oxo_delta_8_tetrahydrocannabinol_in_mice_ L2 - http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&pmid=6113937 DB - PRIME DP - Unbound Medicine ER -