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Biomedical subjects

A L Misra

Publications and source records attributed to A L Misra.

At least 19 recordsLinked to original sources
PubMed1979

Metabolism of norcocaine, N-hydroxy norcocaine and cocaine-N-oxide in the rat.

1. The metabolism of [3H]norcocaine, N-hydroxy[3H]norcocaine and cocaine-N-oxide has been investigated in rats after i.v. injection. 2. The biological t 1/2 of norcocaine (dose 2 mg/kg i.v.) in plasma, liver and brain were 0.4, 1.6, 0.5 h, respectively and the compound was not detectable in the central nervous system 6 h after injection. The % dose of norcocaine excreted unchanged in urine and faeces in 96 h were 0.7 and 1.0, respectively. Benzoylnorecgonine, norecgonine, norecgonine methyl ester and an unidentified compound were excreted in urine. 3. The biological t 1/2 of N-hydroxynorcocaine (5 mg/kg i.v.) in brain and plasma were 0.3, 1.6 h respectively and only 1.3 and 1.6% of dose were excreted unchanged in urine and faeces in 96 h. N-Hydroxybenzoylnorecgonine and N-hydroxynorecgonine methyl ester were the major urinary metabolites. N-hydroxynorcocaine was not metabolized to norcocaine in vitro by liver microsomes. Doses of greater than 7.5 mg/kg i.v. resulted in death of rats by cardiorespiratory arrest. 4. Cocaine-N-oxide (50 mg/kg i.v.) yielded ecgonine-N-oxide methyl ester as its major metabolite; other minor metabolites were cocaine (0.5%), norcocaine (1%), benzoylecgonine, ecgonine, ecgonine-N-oxide, along with minor amounts of unmetabolized compound. Lethality of cocaine-N-oxide (100 mg/kg i.v.) was possibly due to metabolism to norcocaine and cocaine.

Animals↗
PubMed1979

Persistence of phencyclidine (PCP) and metabolites in brain and adipose tissue and implications for long-lasting behavioural effects.

PCP and its new metabolites persisted for very prolonged periods in rat brain and adipose tissue after a single 25 mgkg-1 intraperitoneal injection and showed accumulation after multiple dosing. The brain to plasma ratios for PCP between 0.5 h to 48 h after injection ranged between 6 to 8.8 and adipose tissue to plasma ratios between 31 to 113. The concentrations of metabolites of PCP in rat brain (ng-eqt/g. tissue) 1, 2 and 3 weeks after a single 25 mgkg-1 i.p. injection of PCP were approximately 390, 230 and 74 respectively and those of PCP 12, 6 and 5 ng/g. respectively. The long sojourn of PCP in adipose tissue and relatively slow egress therefrom explains cumulative effects upon multiple dosing and raises the possibility of mobilisation or release of large amounts of drug from fat stores in situations involving food deprivation, marked weight loss or stress. The persistence of PCP and its metabolites in brain and high degree of binding with melanin, implying a possible localisation in neuromelanin-rich substantia nigra of midbrain and locus coeruleus of pons may help explain the prolonged duration of clinical effects and persistent neurological and cognitive dysfunction several days after PCP administration.

Adipose Tissue↗
PubMed1978

Comparative effects of cocaine and pseudococaine on EEG activities, cardiorespiratory functions, and self-administration behavior in the rhesus monkey.

The effects of cocaine and pseudococaine on the EEGs, heart and respiratory rates, and self-administration behavior were studied in rhesus monkeys. An intravenous injection of cocaine (2.5 and 4.0 mg/kg) in the monkey produced low-voltage fast waves (LVFWs) in the EEGs and behavioral hyperexcitation accompanied by marked increases in the heart and respiratory rates with mydriasis and excessive salivation. In contrast, pseudococaine produced high-voltage slow waves (HVSWs) in the EEGs and behavioral depression accompanied by the same symptoms of the autonomic functions as those produced by cocaine. Both isomers were self-administered by the monkeys. During cocaine self-administration sessions, the animals showed hyperexcitation in their overall behavior, while with pseudococaine they showed almost normal behavioral responses. These results suggest that cocaine produced excitatory effects and pseudococaine inhibitory effects on the EEGs and behavior. Both isomers stimulate the heart and respiratory rates, and were self-administered by the monkeys.

Animals↗
PubMed1978

Plasma corticosteroid levels in rats maintained on a long-acting naltrexone delivery system.

A long-acting delivery system for naltrexone has been described, which blocked the antinociceptive action of 10 mg kg-1 s.c. dose of morphine in rats for a period of 2 to 3 months. Male Wistar rats implanted s.c. with such a delivery system showed highly significant depression of plasma corticosteroid levels (40.2% in one week and 22.4 to 27.2% in 3 months) as compared to placebo pellet-implanted animals. Morphine-dependent male rats implanted with 75 mg morphine pellets showed a small (17.5%) but significant increase in plasma corticosteroid levels as compared to the placebo controls 72 hr. after pellet implantation.

Adrenal Cortex Hormones↗
PubMed1977

Severe toxicity and lethality in some monkeys following chronic administration of levo-alpha-acetylmethadol (LAAM).

Recurrent episodes of mild to severe opiate-like toxic effects were observed in 3 of 18 monkeys maintained on 2 mg/kg p.o. dose of LAAM on alternate days 3 times a week for up to one year. Despite antagonist administration and artificial respiration, the final toxic reaction in 3 LAAM sensitive monkeys progressed rapidly to cardio-respiratory arrest and death 3, 6, and 12 months after LAAM treatment. The blood chemistry and hematology were not significantly altered during chronic LAAM administration. Necropsy did not reveal any aberrant gross, histological or neuropathological features other than pulmonary edema. Differential rates of formation and elimination of active metabolites of LAAM may play a significant role in this potentially lethal toxicity. These findings may have important clinical implications for LAAM maintenance treatment programs.

Animals↗
PubMed1977

Evidence for a noncovalent intermolecular interaction of opiates with thiamine.

Opiate agonists and antagonists formed reversible molecular complexes with thiamine. The absorption maxima of these complexes were at wavelengths longer than those of the individual components and their intensities depended on the concentration and nature of the opiate component. The possible implications of such an interaction are discussed.

Chemical Phenomena↗
PubMed1976

[3H]-Noncocaine and [3H]-pseudococaine: effect of N-demethylation and C2-epimerization of cocaine on its pharmacokinetics in the rat.

After i.v. injections of cocaine, norcocaine, pseudococaine to the rat, the T 1/2 in brain were 0.4, 0.6, 0.2 h respectively and in plasma 0.4, 0.5, 0.2 h respectively. Benzoylnorecgonine and norecgonine were the metabolites of norcocaine in brain. Pseudonorcocaine, pseudobenzoylnorecgonine, pseudobenzoylecgonine and pseudoecgonine were the metabolites of pseudococaine in rat brain. Benzolynorecgonine and pseudobenzoylecgonine had potent stimulant activity intracisternally in the rats.

Animals↗