Effects of repeated administration with CP-55,940, a cannabinoid CB1 receptor agonist on the metabolism of the hepatic heme.
Drugs metabolised by cytochrome P450 (CYP) such as analgesics may induce acute attacks in patients with hepatic porphyrias. In recent years, preclinical and clinical studies have suggested that cannabinoid pharmaceutical preparations may be potentially useful in the treatment of pain. The purpose of the study was to examine the effects of CP-55,940, a cannabinoid CB1 receptor agonist, on the hepatic heme metabolism in mice. To this end, hepatic activities of aminolevulinic acid synthase (ALAS), heme oxygenase (HO) and CYP levels were determined in mice treated with CP-55,940 (0.5 mg/kg/day; i.p.; 5 or 24 days). Results showed that treatment with CP-55,940 decreased CYP concentrations by 80% and increased HO activity by 158%. However, ALAS activity also decreased by 37%, suggesting that regulatory free heme pool was not modified. Our findings indicate that CP-55,940 and its metabolites do not behave as porphyrinogenic drugs and may potentially be safe for treating pain in patients with acute porphyrias.
Fontanellas
Antonio
A
Research Center, Hospital Universitario 12 de Octubre, Madrid, Spain.
Manzanares
Jorge
J
García-Bravo
María
M
Buzaleh
Ana María
AM
Méndez
Manuel
M
Oliva
José María
JM
Batlle
Alcira
A
Palomo
Tomas
T
Enríquez de Salamanca
Rafael
R
D000818:Animals; D003511:Cyclohexanols / Q000008:administration & dosage*; D006418:Heme / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists*
D003511:Cyclohexanols; D043884:Receptor, Cannabinoid, CB1; D006418:Heme; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol