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Tryptamine-induced myoclonus in guinea-pigs pretreated with a monoamine oxidase inhibitor indicates pre- and post-synaptic actions of tryptamine upon central indoleamine systems.

Abstract
Tryptamine (1-320 mg/kg) evoked only slight muscle jerking in naive guinea-pigs but, in animals pretreated with pargyline (75 mg/kg; 1 hr previously), tryptamine induced a dose-dependent (6-160 mg/kg) myoclonus. The myoclonus induced by tryptamine (40 mg/kg) plus pargyline (75 mg/kg) was differentially inhibited by the indoleamine receptor antagonists, methergoline (5 mg/kg) which was more potent than methysergide (10 mg/kg), mianserin (10 mg/kg) which was more potent that cyproheptadine (10 mg/kg) and propranolol (20 mg/kg) which was more potent than cinanserin (10 mg/kg). This rank order of potency differed from that observed for the order of potency of these drugs in inhibiting the myoclonus induced by L-5-hydroxytryptophan (5HTP) plus carbidopa in guinea-pigs (Luscombe, Jenner and Marsden, Neuropharmacology, 1981), perhaps indicating involvement of pharmacologically distinct indoleamine receptors. Manipulation of presynaptic function of 5-hydroxytryptamine (5HT) by tryptophan hydroxylase inhibition with p-chlorophenylalanine to produce depletion of cerebral 5HT, or by an L-tryptophan load to elevate 5HT in brain, suggested that the functional integrity of serotonergic neurones is required for the expression of myoclonus induced by tryptamine plus pargyline. A range of blockers of 5HT re-uptake did not alter the jerking produced by tryptamine (40 mg/kg) in guinea pigs pretreated with pargyline (75 mg/kg; 1 hr previously), or the threshold myoclonus induced by a smaller dose of tryptamine (10 mg/kg; plus pargyline 75 mg/kg). It is suggested that myoclonus induced by tryptamine in guinea pigs pretreated with pargyline involves activation of post-synaptic indoleamine receptors by tryptamine by a mechanism which requires intact presynaptic function of 5HT.
AuthorsG Luscombe, P Jenner, C D Marsden
JournalNeuropharmacology (Neuropharmacology) Vol. 21 Issue 12 Pg. 1257-65 (Dec 1982) ISSN: 0028-3908 [Print] ENGLAND
PMID6130489 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Monoamine Oxidase Inhibitors
  • Neurotransmitter Agents
  • Tryptamines
  • Serotonin
  • Pargyline
  • 5-Hydroxytryptophan
  • Tryptophan Hydroxylase
Topics
  • 5-Hydroxytryptophan (pharmacology)
  • Animals
  • Behavior, Animal (drug effects)
  • Female
  • Guinea Pigs
  • Monoamine Oxidase Inhibitors (pharmacology)
  • Myoclonus (chemically induced)
  • Neurotransmitter Agents (metabolism)
  • Pargyline (pharmacology)
  • Serotonin (pharmacology)
  • Synapses (drug effects)
  • Tryptamines (metabolism, pharmacology)
  • Tryptophan Hydroxylase (metabolism)

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