Psychotropic Drug Metabolism in Fetal Alcohol Syndrome
Simultaneous intake of ethanol with chlorpromazine (thorazine), an antipsychotic drug, leads to about 60% decrease in the chlorpromazine removal from the rat blood. Studies with liver homogenates showed that ethanol inhibits the metabolism of this drug by about 50%. The inhibitory effect of ethanol on the metabolism of chlorpromazine can be largely abolished by pyrazole (2 mM) preincubation. Prolonged maternal ethanol consumption during pregnancy and lactation leads to a decrease in chlorpromazine metabolism in the fetal (30%), neonatal (46%) and maternal livers. Prolonged maternal ethanol intake also leads to an increase in the (UDPG)/(UDPGA) ratio in the suckling neonatal liver and the maternal liver. Simultaneous acute administration of ethanol (2g/kg) with psychotropic drugs such as chlordiazepoxide (librium), diazepam (valium), chlorpromazine (thorazine) or meprobamate (equanil) to pregnant or non-pregnant rats led to a decrease in the blood alcohol clearance rates. In another group of nonpsychotropic drugs tested, tolbutamide (orinase) produced the most pronounced (47%) decrease in blood alcohol clearance rates. This decrease was found to be accompanied by the inhibition of hepatic alcohol dehydrogenase.
KeywordsPsychotropic Drug Fetal Alcohol Syndrome Ethanol Metabolism Maternal Liver Maternal Alcohol Consumption
Unable to display preview. Download preview PDF.
- Haux, P., and Natelson, S., 1976, A practical method for the assay of phenothiazines in biologic fluids, Am. J. Clin. Path. 53:77–83.Google Scholar
- Henderson, G.I., and Schenker, S., 1977, The effects of maternal alcohol consumption on the viability and visceral development of the newborn rat, Res. Comm. Chem. Path. Pharm. 16:15.Google Scholar
- Lemoine, P., Harousseau, H., Borteyru, J.P., and Meneut, J.C., 1968, Les enfants de parents alcoholiques. A propose de 127 cas, Quest Medical 25: 477.Google Scholar
- Linnoila, M., and Hakkinen, S., 1974, Effects of diazepam and codeine alone or in combination with alcohol on simulated driving, Clin. Pharmacol. Ther. 15:368.Google Scholar
- Mills, G.T., and Smith, E.B., 1965, Uridine diphosphoglucose, uridine diphosphogalactase, uridine triphosphate and uridine diphosphoglucuroric acid, in: “Methods of Enzymatic Analysis,” pp. 581, H.U. Bergmeyer, ed., Academic Press, New York.Google Scholar
- Rawat, A.K.; 1968, Effects of ethanol infusion on the redox-state and metabolite levels in rat liver in vivo, Eur. J. Biochem. 6:585.Google Scholar
- Rawat, A.K., 1976, Effects of materbal ethanol consumption on fetal hepatic metabolism in the rat, Ann. N.Y. Acad. Sci. 273:175.Google Scholar
- Rawat, A.K., and Lundquist, F., 1968, Influence of thyroxine on the metabolism of ethanol and glycerol in rat liver slices, Eur. J. Biochem. 5:13.Google Scholar
- Veech, R.L., Guynn, R., and Veloso, D., 1972, The time course on the effects of ethanol on the redox and phosphorylation states of rat liver, Biochem. J. 127:38.7.Google Scholar