TY - JOUR
T1 - Comparative Activity of Dihydrocodeine and Its Metabolites in the Electrically Stimulated Guinea‐pig Isolated Ileum
AU - Kirkwood, Lynette C..
AU - Venning, Michael G.
AU - Nation, Roger L.
AU - Reynolds, Geoffrey D
AU - Somogyi, Andrew A.
AU - Sansom, Lloyd N.
PY - 1995/1/1
Y1 - 1995/1/1
N2 - The pharmacological potencies of dihydrocodeine and its metabolites, dihydrocodeine‐6‐glucuronide, nordihydrocodeine and dihydromorphine, were compared with morphine and codeine by measuring the influence on electrically stimulated contractions in the guinea‐pig isolated ileum. The mean (± standard error) EC50 of dihydromorphine (23 ± 3 nM) was similar to morphine (33 ± 3 nM) and these compounds were approximately 100 times more potent than dihydrocodeine (2660 ± 320 nM), nordihydrocodeine (2760±180 nM) and dihydrocodeine‐6‐glucuronide (2120 ± 230 nM). Dihydrocodeine and codeine were equipotent. These results suggest that dihydromorphine is a potent active metabolite of dihydrocodeine. Dihydromorphine formation from dihydrocodeine is catalysed by the polymorphically expressed cytochrome P450 2D6 in man; hence analgesia from dihydrocodeine may be dependent on expression of polymorphic CYP2D6. 1995 Royal Pharmaceutical Society of Great Britain
AB - The pharmacological potencies of dihydrocodeine and its metabolites, dihydrocodeine‐6‐glucuronide, nordihydrocodeine and dihydromorphine, were compared with morphine and codeine by measuring the influence on electrically stimulated contractions in the guinea‐pig isolated ileum. The mean (± standard error) EC50 of dihydromorphine (23 ± 3 nM) was similar to morphine (33 ± 3 nM) and these compounds were approximately 100 times more potent than dihydrocodeine (2660 ± 320 nM), nordihydrocodeine (2760±180 nM) and dihydrocodeine‐6‐glucuronide (2120 ± 230 nM). Dihydrocodeine and codeine were equipotent. These results suggest that dihydromorphine is a potent active metabolite of dihydrocodeine. Dihydromorphine formation from dihydrocodeine is catalysed by the polymorphically expressed cytochrome P450 2D6 in man; hence analgesia from dihydrocodeine may be dependent on expression of polymorphic CYP2D6. 1995 Royal Pharmaceutical Society of Great Britain
UR - http://www.scopus.com/inward/record.url?scp=84988168692&partnerID=8YFLogxK
U2 - 10.1111/j.2042-7158.1995.tb00382.x
DO - 10.1111/j.2042-7158.1995.tb00382.x
M3 - Article
AN - SCOPUS:84988168692
SN - 1460-8081
VL - 1
SP - 573
EP - 575
JO - Pharmacy and Pharmacology Communications
JF - Pharmacy and Pharmacology Communications
IS - 12
ER -