Separation of hepatic n-demethylase-inducing and opioid dependence-producing doses of levo-alpha-acetylmethadol in the pregnant rat

S. D. Mercurio; L. Lichtblau; S. B. Sparber

doi:10.1016/0024-3205(83)90016-4

Separation of hepatic n-demethylase-inducing and opioid dependence-producing doses of levo-alpha-acetylmethadol in the pregnant rat

S. D. Mercurio, L. Lichtblau, S. B. Sparber

Basic Sciences

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Abstract

A 2.0 mg per kg oral dose of l-alpha-acetylmethadol (LAAM) administered daily to female rats prior to mating and throughout pregnancy increased ethylmorphine N-demethylase activity in liver microsomes of the dams measured 24 h after parturition. This dose of LAAM decreased maternal weight gain during gestation and increased postnatal mortality. However, 0.05 mg LAAM per kg was sufficient to produce dependence in the dams without affecting hepatic drug metabolism, gestational weight gain or neonatal mortality. The data indicate that it is not necessary to use doses of LAAM which can affect drug metabolizing enzymes in dams and increase pup mortality to maintain opioid-type physical dependence.

Original language	English (US)
Pages (from-to)	1127-1134
Number of pages	8
Journal	Life Sciences
Volume	33
Issue number	12
DOIs	https://doi.org/10.1016/0024-3205(83)90016-4
State	Published - Sep 19 1983

Bibliographical note

Funding Information:
This study was supported by USPHS grants DA01880 and 5T32DA07097. We thank Dr. G. J. Mannering for the use of the Aminco DW2-dual beam spectrophotometer and Dr. E. Jeffrey for her helpful comments. We also wish to thank Jackie Dokken for the preparation of this manuscript.

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title = "Separation of hepatic n-demethylase-inducing and opioid dependence-producing doses of levo-alpha-acetylmethadol in the pregnant rat",

abstract = "A 2.0 mg per kg oral dose of l-alpha-acetylmethadol (LAAM) administered daily to female rats prior to mating and throughout pregnancy increased ethylmorphine N-demethylase activity in liver microsomes of the dams measured 24 h after parturition. This dose of LAAM decreased maternal weight gain during gestation and increased postnatal mortality. However, 0.05 mg LAAM per kg was sufficient to produce dependence in the dams without affecting hepatic drug metabolism, gestational weight gain or neonatal mortality. The data indicate that it is not necessary to use doses of LAAM which can affect drug metabolizing enzymes in dams and increase pup mortality to maintain opioid-type physical dependence.",

author = "Mercurio, {S. D.} and L. Lichtblau and Sparber, {S. B.}",

note = "Funding Information: This study was supported by USPHS grants DA01880 and 5T32DA07097. We thank Dr. G. J. Mannering for the use of the Aminco DW2-dual beam spectrophotometer and Dr. E. Jeffrey for her helpful comments. We also wish to thank Jackie Dokken for the preparation of this manuscript.",

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T1 - Separation of hepatic n-demethylase-inducing and opioid dependence-producing doses of levo-alpha-acetylmethadol in the pregnant rat

AU - Mercurio, S. D.

AU - Lichtblau, L.

AU - Sparber, S. B.

N1 - Funding Information: This study was supported by USPHS grants DA01880 and 5T32DA07097. We thank Dr. G. J. Mannering for the use of the Aminco DW2-dual beam spectrophotometer and Dr. E. Jeffrey for her helpful comments. We also wish to thank Jackie Dokken for the preparation of this manuscript.

PY - 1983/9/19

Y1 - 1983/9/19

N2 - A 2.0 mg per kg oral dose of l-alpha-acetylmethadol (LAAM) administered daily to female rats prior to mating and throughout pregnancy increased ethylmorphine N-demethylase activity in liver microsomes of the dams measured 24 h after parturition. This dose of LAAM decreased maternal weight gain during gestation and increased postnatal mortality. However, 0.05 mg LAAM per kg was sufficient to produce dependence in the dams without affecting hepatic drug metabolism, gestational weight gain or neonatal mortality. The data indicate that it is not necessary to use doses of LAAM which can affect drug metabolizing enzymes in dams and increase pup mortality to maintain opioid-type physical dependence.

AB - A 2.0 mg per kg oral dose of l-alpha-acetylmethadol (LAAM) administered daily to female rats prior to mating and throughout pregnancy increased ethylmorphine N-demethylase activity in liver microsomes of the dams measured 24 h after parturition. This dose of LAAM decreased maternal weight gain during gestation and increased postnatal mortality. However, 0.05 mg LAAM per kg was sufficient to produce dependence in the dams without affecting hepatic drug metabolism, gestational weight gain or neonatal mortality. The data indicate that it is not necessary to use doses of LAAM which can affect drug metabolizing enzymes in dams and increase pup mortality to maintain opioid-type physical dependence.

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Separation of hepatic n-demethylase-inducing and opioid dependence-producing doses of levo-alpha-acetylmethadol in the pregnant rat

Abstract

Bibliographical note

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