Morphine inhibition of drug metabolism in the rat

Bousquet, William F.; Rupe, Billy D.; Miya, Tom S.

doi:10.1016/0006-2952(64)90088-7

Cited by 20 publications

(6 citation statements)

References 8 publications

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“…These data indicate that dependence on morphine does not consistently inhibit the in vitro hepatic clearance of morphine in the rat. These findings are in contrast with previous reports (4).…”

Section: The Effect O F Morphine Dependence On the In Vitro Hepatic Ccontrasting

confidence: 57%

“…Chronic morphine administration has been reported to inhibit both oxidative and conjugative metabolism in the rat (4). In the present study, it was of interest to determine if depen dence on morphine in the rat consistently in hibited the in vitro hepatic clearance of mor phine by the 9,000 g supernatant.…”

Section: The Effect O F Morphine Dependence On the In Vitro Hepatic Cmentioning

confidence: 99%

“…Brains and plasma of morphine-de pendent male and female rats (4 days) were The results of these studies (table I) indicate that rat whole brain concentrations of mor phine fluctuated over a wide range in both male (59.9-184. 4 ng/g brain) and female (47.5-200.7 ng/g brain) rats. Two-way analysis of variance (F = 4.11; d.f.…”

Section: Long-term Variation In Brain Concentrations O F Morphinementioning

confidence: 99%

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Evidence of a Long-Term Rhythm in Withdrawal, Brain Concentration, and Hepatic Clearance of Morphine in the Rat

Williams¹,

Spratto²

1978

Pharmacology

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The technique of morphine pellet implantation was utilized to produce physical dependence on morphine in both male and female rats. At the peak of dependence (96 h), naloxone hydrochloride (1.0 mg/kg s.c.) was administered to precipitate withdrawal and the mean number of ‘wet dog’ shakes was determined for 30 min. A predictable and rhythmic cycle of approximately 6 weeks was observed in the number of ‘wet dog’ shakes in morphine-withdrawn animals. This rhythm was not a sex-related phenomenon; there was no discernable rhythm in total body weight loss during the withdrawal period. The intensity of the withdrawal response was inversely related to the brain concentration of morphine. However, the periodicity of the long-term rhythm in ‘wet dog’ shakes was not similar to that of brain concentrations of morphine. An 8 month study of the in vitro hepatic clearance of morphine in the nondependent rat indicated that there are long-term fluctuations in the rate at which morphine is cleared from the rat liver. Also, development of dependence on morphine in the rat was not found to consistently alter the hepatic clearance of the drug. These findings suggest more than one controlling mechanism in the fluctuation of ‘wet dog’ shakes and that the time of the year at which the study is conducted is an important variable in the determination of the effects of morphine dependence in the rat.

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Section: The Effect O F Morphine Dependence On the In Vitro Hepatic Ccontrasting

confidence: 57%

Section: The Effect O F Morphine Dependence On the In Vitro Hepatic Cmentioning

confidence: 99%

Section: Long-term Variation In Brain Concentrations O F Morphinementioning

confidence: 99%

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Evidence of a Long-Term Rhythm in Withdrawal, Brain Concentration, and Hepatic Clearance of Morphine in the Rat

Williams¹,

Spratto²

1978

Pharmacology

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“…With the opiates, chronic drug administration does not induce hepatic drug-metabolizing enzyme activity, the tolerance being due entirely to adaptive changes (Bousquet, Rupe & Miya, 1964;Adler, 1967). In the case of the barbiturates, enzyme induction is usually responsible for the observed tolerance, but after prolonged exposure to high drug concentrations a central cellular tolerance may also be a contributory factor.…”

Section: Discussionmentioning

confidence: 99%

A Study of the Factors Affecting the Sleeping Time Following Intracerebroventricular Administration of Pentobarbitone Sodium: Effect of Prior Administration of Centrally Active Drugs

Stevenson

Bull

1974

British J Pharmacology

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1 Injection of pentobarbitone sodium into a lateral cerebral ventricle of rats produced a loss of righting reflex. The duration of anaesthesia was dose-dependent. 2 The optimum dose of pentobarbitone to allow study of the factors affecting the sleeping time was considered to be 650 ,ug injected in 25 M water. 3 In a study of the effect of age and sex on the sleeping time, the youngest rats used (88 g body weight) were found to be the most sensitive to barbiturate. Female rats were more sensitive than male animals. 4 The duration of anaesthesia was not affected by induction or inhibition of hepatic drug-metabolizing enzyme activity. 5 Prior administration (acute) of central nervous system depressant drugs shortened the latent period and prolonged the duration of sleep. Prior administration of stimulant drugs antagonized the effect of pentobarbitone. 6 Animals withdrawn following chronic administration of a number of drugs, barbitone, barbitone/bemegride mixture, Mandrax (methaqualone: diphenhydramine; 10: 1), chlordiazepoxide, nitrazepam, chlorpromazine or ethanol, exhibited a significant tolerance to intracerebroventricularly administered pentobarbitone. 7 Withdrawal of amphetamine, morphine, methyprylon or diazepam did not result in tolerance to intracerebroventricularly administered pentobarbitone. 8 Chronic administration of all drugs except amphetamine and morphine induced a tolerance to intraperitoneally administered hexobarbitone (100 mg/kg). 9 The usefulness of sleeping time determination following intracerebroventricular administration of pentobarbitone as an assessment of central nervous system excitability is discussed. It is concluded that this method gives a valid indication of the sensitivity of the central nervous system to barbiturate and of the level of excitability in general. The method is particularly applicable in situations where the activity of hepatic drug-metabolizing enzyme activity may be altered.

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“…Effect of analgesics on barbiturate metabolism.-Pretreatment of rats with morphine (20 mg/kg intraperitoneally daily for four days) increased the duration of hexobarbital hypnosis, but had no effect on the hypnotic action of barbital (72). Hexobarbital and morphine metabolism were studied in liver slice preparations from control and morphine pretreated rats.…”

Section: Drug Interactionmentioning

confidence: 99%

Metabolic Fate of Drugs: Barbiturates and Closely Related Compounds

Bush¹,

Sanders²

1967

Annu. Rev. Pharmacol.

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The literature on drug metabolism has been increasing so rapidly that it is clearly impossible in the present article to cover more than a very narrow area of the subject. There are a number of recent comprehensive papers or reviews (1-7) . In order to avoid undue repetition (which is indeed difficult!) the authors have chosen to focus their attention on the barbiturates and certain closely related compounds, an area which apparently has not been brought up to date since the reviews of Williams & Parke (8) and Mark (9). The moderate number of papers which have appeared since about mid-1963 will be reviewed from two points of view: the specific chemical alterations brought about by metabolic systems, and the influence of pretreatment with the same or another drug on the rates of these enzymatic reactions. Both in vitro and in vivo studies will be considered. The many physiological factors which have been shown to affect drug metabolism (age, sex, heredity, species and strain, state of health, etc.) will not be discussed. Extensive papers on most of these subjects have recently appeared (10-13).Since it is so important an aspect of the subject, qualitative and quan titative methodology will be discussed in relation to some of the recent im provements in techniques for the detection and estimation of barbiturates and their metabolites in biological material. METHODOLOGYThe detection and estimation of barbiturates and closely related drugs and their metabolites continue to receive much attention, clearly because no satisfactory comprehensive systematic procedures have yet been devel oped. Paper, thin-layer, and now gas chromatography have become increas ingly popular. The older (classical) procedures involving recovery by solvent extraction, purification by systematic multiple extractions, or countercurrent distribution (CCD), followed by identification and quantitation by ultra violet spectrophotometry, have never been developed to their fullest poten tial. It would seem that coordination of the "classical" procedures with one or another of the chromatographic techniques will be necessary if a satis factory methodology is to be worked out. Most recent authors have focused 1 The survey of the literature pertaining to this review was concluded June 30, 1966.

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Morphine inhibition of drug metabolism in the rat

Cited by 20 publications

References 8 publications

Evidence of a Long-Term Rhythm in Withdrawal, Brain Concentration, and Hepatic Clearance of Morphine in the Rat

Evidence of a Long-Term Rhythm in Withdrawal, Brain Concentration, and Hepatic Clearance of Morphine in the Rat

A Study of the Factors Affecting the Sleeping Time Following Intracerebroventricular Administration of Pentobarbitone Sodium: Effect of Prior Administration of Centrally Active Drugs

Metabolic Fate of Drugs: Barbiturates and Closely Related Compounds

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