In vivo PHARMACOLOGICAL STUDIES ON THE INTERACTIONS BETWEEN TRYPTAMINE AND 5‐HYDROXYTRYPTAMINE

Jones, Roland S.G.

doi:10.1111/j.1476-5381.1981.tb10447.x

Cited by 40 publications

(2 citation statements)

References 22 publications

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“…It has been speculated that tryptamine might be a neuromodulator, perhaps opposing the actions of serotonin (5-hydroxytryptamine; 5-HT) and, thus, playing a role in the regulation of mood, emotion, sleep, and appetite (Jones, 1981(Jones, , 1982, the cardinal functions of 5-HT. Elevated tryptamine urinary excretion has been observed in schizophrenic patients, attributed to low MAO activity (Sullivan et al, 1980).…”

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confidence: 99%

The Relative Contribution of Monoamine Oxidase and Cytochrome P450 Isozymes to the Metabolic Deamination of the Trace Amine Tryptamine

Yu¹,

Granvil²,

Haining³

et al. 2003

J Pharmacol Exp Ther

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Tryptamine is a trace amine in mammalian central nervous system that interacts with the trace amine TA 2 receptor and is now thought to function as a neurotransmitter or neuromodulator. It had been reported that deamination of tryptamine to tryptophol was mediated by CYP2D6, a cytochrome P450 that is expressed in human brain, suggesting that tryptamine may be an endogenous substrate for this polymorphic enzyme. We were unable to confirm this report and have reinvestigated tryptamine metabolism in human liver microsomes (HLM) and in microsomes expressing recombinant human cytochrome P450 and monoamine oxidase (MAO) isozymes. Tryptamine was oxidized to indole-3-acetaldehyde by HLM and recombinant human MAO-A in the absence of NADPH, and indole-3-acetaldehyde was further reduced to tryptophol by aldehyde reductase in HLM in the presence of NADPH. Steady-state kinetic parameters were estimated for each reaction step by HLM and MAO-A. The CYP2D6 substrates bufuralol and debrisoquine showed strong inhibition of both tryptophol production from tryptamine in HLM and the formation of indole-3-acetaldehyde from tryptamine catalyzed by recombinant MAO-A. Anti-CYP2D6 monoclonal antibody did not inhibit these reactions. Pargyline, a nonselective MAO inhibitor, did not show cross inhibition to debrisoquine 4-hydroxylation and dextromethorphan O-demethylation by HLM and recombinant CYP2D6 enzyme. This is the first unequivocal report of the selective conversion of tryptamine to tryptophol by MAO-A. CYP2D6 does not contribute to this reaction.

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confidence: 99%

The Relative Contribution of Monoamine Oxidase and Cytochrome P450 Isozymes to the Metabolic Deamination of the Trace Amine Tryptamine

Yu¹,

Granvil²,

Haining³

et al. 2003

J Pharmacol Exp Ther

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“…It seemed possible that these responses were mediated by two different receptor populations within the preoptic anterior hypothalamus since they had different susceptibilities to blockade by indoleamine-receptor antagonists (Cox, Lee & Martin, 1981). Recently, results from behavioural (Jones, 1981) and ionophoretic studies (Jones & Boulton, 1980) have suggested that tryptamine may modulate central 5-HT activity. Therefore, it was of interest to attempt to determine whether 5-HT and tryptamine acted in the same or separate pathways to produce their respective changes in core temperature.…”

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A role for an indoleamine other than 5‐hydroxytryptamine in the hypothalamic thermoregulatory pathways of the rat

Cox

Davis

Juxon

et al. 1983

The Journal of Physiology

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1. Intrahypothalamic injection of either 5‐hydroxytryptamine (5‐HT) (20 μg) or tryptamine (1 μg) caused hypothermia and hyperthermia respectively in lightly restrained rats maintained at an ambient temperature of 20 ± 1 °C. 2. Both the 5‐HT‐ and the tryptamine‐sensitive sites were located within the same region of the preoptic area. 3. When rats were tested at different ambient temperatures (4, 20 and 29 °C), intrahypothalamic injection of 5‐HT caused a marked fall in core temperature (‐1·3 °C) in rats maintained at 4 °C, but smaller responses were obtained at 20 and 29 °C (‐0·9 and ‐0·5 °C respectively). Tryptamine caused a significant hyperthermia in rats kept at 20 °C, but had no significant effect in rats maintained at either 4 or 29 °C. 4. The hypothermic effect of 5‐HT was selectively antagonized by systemic pre‐treatment with cyproheptadine (2·5 mg/kg), but not by methergoline (0·625 mg/kg) and methysergide (0·2 mg/kg). In contrast, the hyperthermic effect of tryptamine was blocked by methergoline and methysergide, but not by cyproheptadine. 5. Cyproheptadine (2·5 mg/kg) reduced the ability of rats to cope with a heat load but had no effect on the response to cold. In contrast, methergoline (0·625 mg/kg) and methysergide (0·2 mg/kg) reduced the ability to cope with cold but the rats' ability to cope with a heat load remained intact. 6. These results suggest the existence of two indoleamine pathways within the preoptic anterior hypothalamus involved in the control of body temperature: a serotonergic pathway mediating heat loss and a non‐serotonergic pathway mediating heat gain. The non‐serotonergic system may exert its effects by modulating the activity of a central serotonergic system.

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Agents Acting on Prostanoid Receptors

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Humphrey

Coleman³

2003

Burger's Medicinal Chemistry and Drug Discovery

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The prostaglandins and thromboxanes comprise a family of C 20 fatty acids, known as the prostanoids. They are primarily synthesized from arachidonic acid and exert a multitude of physiological and pathophysiological actions through the activation of membrane‐bound receptors. The current scheme of prostanoid receptor classification proposes receptors for each of the naturally occurring prostanoids and was originally based on comparisons of prostanoid receptor agonist and antagonist potencies in functional preparations. This scheme has been confirmed and expanded by the use of molecular techniques, which have led to the cloning of the known prostanoid receptors and also the discovery of a number of prostanoid receptor subtypes and isoforms. Many compounds with varying potencies and selectivities at the known prostanoid receptors have been synthesized, although few have proved highly valuable in the clinic. The use of prostanoids in clinical practice has been largely limited to those occurring naturally, where they are used predominantly as abortifacients and in the induction of labor. Several synthetic analogs have also been used for these and other purposes, including the treatment of gastric ulcers and glaucoma. Hopefully, the next few years will lead to the further discovery of new prostanoid receptor ligands that will become successful medicines.

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In vivo PHARMACOLOGICAL STUDIES ON THE INTERACTIONS BETWEEN TRYPTAMINE AND 5‐HYDROXYTRYPTAMINE

Cited by 40 publications

References 22 publications

The Relative Contribution of Monoamine Oxidase and Cytochrome P450 Isozymes to the Metabolic Deamination of the Trace Amine Tryptamine

The Relative Contribution of Monoamine Oxidase and Cytochrome P450 Isozymes to the Metabolic Deamination of the Trace Amine Tryptamine

A role for an indoleamine other than 5‐hydroxytryptamine in the hypothalamic thermoregulatory pathways of the rat

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