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.
Olivera
M
M
Department of Pharmacology, Medical School, University of Extremadura, Badajoz, Spain.
Martínez
C
C
Gervasini
G
G
Carrillo
J A
JA
Ramos
S
S
Benítez
J
J
García-Martin
E
E
Agúndez
J A G
JA
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