The influence of thyroid status on the effects and metabolism of pentobarbital and thiopental

Prange, Arthur J.; Lipton, Morris A.; Shearin, Robert B.; Love, Gennifer

doi:10.1016/0006-2952(66)90294-2

Cited by 24 publications

(3 citation statements)

References 10 publications

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“…This fact invalidates many of the investigations and reduces their value in predicting the behaviour of drugs in man. In male rats and mice the metabolism of hexobarbital (enhexymalum NFN), pentobarbital (mebumalum "N), aminopyrine, morphine and meperidine (pethidinum "N) has been shown in several studies to decrease after administration of thyroxine, while in female rats the turn-over of hexobarbital and aminopyrine is either unaffected or increased by thyroxine (COCHIN & SOKOLOFF 1960; CONNEY & GARREN 1961; KATO & GILLETTE 1965;PRANGE et al 1966;SCHROGIE & SOLOMON 1967). In contrast, the metabolism of aniline is augmented in both sexes after thyroxine treatment (KATO & GILLETTE 1965).…”

Section: Discussionmentioning

confidence: 99%

The Kinetics of Propylthiouracil in Hyperthyroidism

Skovsted

1975

Acta Pharmacologica et Toxicologica

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A bsrrucr: The kinetics of propylthiouracil have been estimated in 10 hyperthyroid subjects according to a two-compartment model by giving the drug initially by the intravenous and subsequently by the oral route. The apparent half-life was 77 f 34 min. (mean k S.D.). This value and other pharmacokmetic parameters were compared with the corresponding values obtained in a previous study in normal subjects. No significant differences were found. A table showing studies in humans correlating drug metabolism and thyroid status is presented.

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Section: Discussionmentioning

confidence: 99%

The Kinetics of Propylthiouracil in Hyperthyroidism

Skovsted

1975

Acta Pharmacologica et Toxicologica

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“…Hyperthyroid animals have been found to be susceptible to the toxicity of some pharmacological agents ; Carrier and Buday (3) have compiled a list of substances whose toxicity was increased by hyperthyroidism. Hypothyroidism and hyperthyroidism delayed the removal of pentobarbital from rat tissues after intravenous administration (7). Administration of thyroxine to rats has been shown to accelerate or inhibit various drug-metabolizing enzymes (5, 6).…”

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confidence: 99%

Barbiturate Mortality in Hypothyroid and Hyperthyroid Rats

Harbison

Becker

1969

Journal of Pharmaceutical Sciences

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“…Since a high prevalence of mental dysfunction exists, and also a concommitant economic loss due to work disability and/or hospitalization, as well as the ever present danger of suicide, a persistent as well as compelling reason to search for a treatment for depression, that is both rapid, safe and convenient becanes necessary. Since treatment with thyroid hormones has been shown to enhance the pharmacological actions of several of the barbiturates (Conney and Garren, 1961;Prange, et al, 1966), and also since other clinical studies (Prange, et al, 1970A;Earle, 1970;Prange, ! !_al., 19708;Wheatley, 1972;Whybrew, et al, 1972;Slusher, 1975;and Schmidt, 1977) as well as some animal investigation (Prange and Lipton, 1962; have documented an increase in drug efficacy, it has been theorized that the thyroid hormones may accelerate the antidepressant actions of the tricyclics or these other pharmacological agents (Cavalieri and Pitt-Rivers, 1981).…”

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The Integrated Relationships of Protriptyline, Thyroid Status and Noradrenergic Mechanisms in Rat Brain

Kaiser¹

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Reasons for the observed lag-time for clinical efficacy of the tricyclic antidepressant drug, protriptyline, have been investigated. t-, • Our results demonstrate that chronic protriptyline administration resulta in several compensatory neural mechanisms: (1) changes in endogeneous cytoplasmic norepinephrine levels, (2) changes in norepinephrine turnover rate/recovery rate following the last dose in a chronic series of test drug administrations and (3) adaptations of the pre-synaptic receptor. The time course for these adaptive changes parallel the time required for the onset of their clinical effectiveness. We propose that acutely the action of the tricyclics on norepinephrine re-uptake is largely negated by compensatory adjustments in turnover rate of the neurotransmitter; but with chronic administration, adaptations in pre-synaptic alpha-receptors occur. This phenomena in turn reduces the extent to which the norepinephrine neurons can offset or compensate for the blockade of norepinephrine re-uptake. Specifically, pre-synaptic alpha-receptors become hyposensitive, and receptor tolerance develops; not to the direct action of the tricyclic drug on neurotransmitter re-uptake, but to the compensatory neural adjustments which offset the action of the acute tricyclic administration and delay their clinical efficacy. OUr results demonstrated that tricyclic antidepressant drugs, when administered chronically, do not alttr monoamine oxidase activity in vivo in any of the three brain regions we examined (corpus striatua, forebrain, and hypothalamus). Similarly, we were not able to identify a noradrengeric relationship other than those that were both toxic and lethal when thyroid hormone was administered with the tricyclic antidepressant drug Protriptyline. We did, however, observe that in the hyperthyroid condition norepinephrine turnover is decreased in hypothalamus when compared to control animals. The results we obtained from chronic protriptyline administration and its effects on norepinephrine levels and turnover, as well as the results we obtained when yohimbine was employed are enlightening. Chronic protriptyline administration produced decreased norepinephrine levels in hypothala11Us, and decreased norepinephrine turnover, when compared to saline administered controls. The alpha-receptor antagonist (yohimbine} produced only minor effects on norepinephrine levels and turnover when experimental animals were pretreated chronically (18 days) with protriptyline. These results suggest an adaptive response (hypo-sensitivity) of the presynaptic alpha-receptor (autoreceptor), and this phenomena also occurs at the post-synaptic alpha-receptor. These results, suggesting receptor adaptation, indicated the existence of another mechanism of action for the tricyclic antidepressants.

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The influence of thyroid status on the effects and metabolism of pentobarbital and thiopental

Cited by 24 publications

References 10 publications

The Kinetics of Propylthiouracil in Hyperthyroidism

The Kinetics of Propylthiouracil in Hyperthyroidism

Barbiturate Mortality in Hypothyroid and Hyperthyroid Rats

The Integrated Relationships of Protriptyline, Thyroid Status and Noradrenergic Mechanisms in Rat Brain

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