Developmental Toxicity of Levo-Alpha-Acetylmethadol (LAAM) in Tolerant Rats
نویسندگان
چکیده
منابع مشابه
Levo-α-acetylmethadol (LAAM) induced QTc-prolongation - results from a controlled clinical trial
BACKGROUND Due to potential proarrhythmic side-effects levo-alpha-Acetylmethadol (LAAM) is currently not available in EU countries as maintenance drug in the treatment of opiate addiction. However, recent studies and meta-analyses underline the clinical advantages of LAAM with respect to the reduction of heroin use. Thus a reappraisal of LAAM has been demanded. The aim of the present study was ...
متن کاملMetabolism of levo-alpha-Acetylmethadol (LAAM) by human liver cytochrome P450: involvement of CYP3A4 characterized by atypical kinetics with two binding sites.
levo-alpha-Acetylmethadol (LAAM) is a long-acting opioid agonist prodrug used for preventing opiate withdrawal. LAAM undergoes bioactivation via sequential N-demethylation to nor-LAAM and dinor-LAAM, which are more potent and longer-acting than LAAM. This study examined LAAM and nor-LAAM metabolism using human liver microsomes, cDNA-expressed CYP, CYP isoform-selective chemical inhibitors, and ...
متن کاملThe involvement of cytochrome P450 3A4 in the N-demethylation of L-alpha-acetylmethadol (LAAM), norLAAM, and methadone.
The N-demethylation of LAAM, norLAAM, and methadone has been investigated in human liver microsomes and microsomes containing cDNA-expressed human P450s. Gas chromatography/mass spectrometry methods allowed detection of norLAAM and dinorLAAM formation from LAAM, dinorLAAM formation from norLAAM, and EDDP and EMDP formation from methadone. The rates of N-demethylation varied 4- to 7-fold in micr...
متن کاملSub-Chronic Toxicity Study of Alpha-Cypermethrin in Rats
Alpha-cypermethrin (?-CP) a synthetic pyrethroid (type-II) insecticide, dissolved in dimethyl sulfoxide (DMSO-1ml) given consecutive daily orally for 60 days at 1/10LD50 (14.5mg/kg). The animals were sacrificed on day 61st. Biochemicals, cytochromeP450, b5 contents in liver along with antioxidant status, tissue residual concentration, and brain GABA level were studied. It increased the serum am...
متن کاملVariables in human liver microsome preparation: impact on the kinetics of l-alpha-acetylmethadol (LAAM) n-demethylation and dextromethorphan O-demethylation.
We examined three primary variables in the preparation of human liver microsomes. In three experiments, each using three livers, we manipulated 1) the force of the first centrifugation (9,000, 10,500, or 12,000g); 2) the presence of sucrose in the homogenization buffer; and 3) the number of homogenizing strokes (6, 8, or 10). Sedimentation plots for the marker enzymes succinate dehydrogenase, N...
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ژورنال
عنوان ژورنال: International Journal of Toxicology
سال: 2002
ISSN: 1091-5818,1092-874X
DOI: 10.1080/10915810252866105