The effect of phenothiazine and dibenzazepine pretreatment on the metabolism of methamphetamine in rats.
There was marked variation between p-hydroxylation and N-demethylation of methamphetamine in rats. Within 24 h, 10.4, 24-7 and 4.1% of the administered methamphetamine was excreted in urine unchanged, p-hydroxymethamphetamine (p-OH-MP, free plus conjugated) and also as amphetamine, respectively. Treatment by imipramine, desipramine, chlorpromazine, perphenazine and propericiazine 8 h before the administration with methamphetamine completely inhibited the urinary excretion of p-OH-MP whereas the excretion of amphetamine was enhanced by about 700 to 800%. This effect was also observed in rats treated with imipramine 16 and 24 h before methamphetamine. Phenothiazine and dibenzazepine derivatives reverse the degree of p-hydroxylation and N-demethylation of methamphetamine in-vivo in rats.
Mori
M
M
Fujita
M
M
Kozuka
H
H
D000661:Amphetamine / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003640:Dealkylation; D003984:Dibenzazepines / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D006900:Hydroxylation; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000378:metabolism*; D010640:Phenothiazines; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D014150:Antipsychotic Agents; D003984:Dibenzazepines; D010640:Phenothiazines; D008694:Methamphetamine; D000661:Amphetamine; D007099:Imipramine