Effect of common NAT2 variant alleles in the acetylation of the major clonazepam metabolite, 7-aminoclonazepam.
We investigated the role of NAT2 on clonazepam acetylation, using transiently expressed human NAT2 alleles. The NAT25*B and the NAT2*6A variant alleles cause a 20 and 22-fold reduction in the Vmax, respectively. We conclude that NAT2 is responsible for 7-aminoclonazepam acetylation and that NAT2 gene polymorphisms impair such metabolic pathway.
Department of Pharmacology, Medical School, University of Extremadura, Badajoz, Spain.
M
M
Olivera
C
C
Martínez
G
G
Gervasini
J A
JA
Carrillo
S
S
Ramos
J
J
Benítez
E
E
García-Martin
J A G
JA
Agúndez
D000107:Acetylation; D000483:Alleles; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D002998:Clonazepam / Q000031:analogs & derivatives* / Q000378:metabolism*; D006801:Humans; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D014162:Transfection
C020860:7-aminoclonazepam; D002998:Clonazepam; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human