Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Indoleamine-induced myoclonus in guinea pigs is a specific model of brainstem 5-HT function that can be used to characterize the indoleamine systems initiating myoclonus. 5-HT precursors and indole-containing 5-HT agonists induce myoclonus in guinea pigs, but piperazine-containing compounds do not. This selectivity of action correlates with the ability of 5-HT agonists to act at 5-HT-1 receptors. Further evidence for the involvement of a brainstem 5-HT receptor subpopulation in the initiation of myoclonus is shown by the differential ability of 5-HT antagonists to inhibit 5-HTP-induced myoclonus and of 5-HT reuptake blockers to potentiate threshold myoclonus. Distinct tryptamine receptors also may be involved in producing myoclonus, since indoleamine antagonists show differing potencies in inhibiting 5-HTP- and tryptamine-induced myoclonus. Tryptamine-induced myoclonus is, however, dependent on intact presynaptic 5-HT function. Biochemical studies indicate that 5-HT is primarily responsible for 5-HTP-evoked myoclonus, whereas tryptamine predominates in tryptamine-induced myoclonus. Both 5-HT and tryptamine may contribute to myoclonus produced by L-tryptophan. Indoleamine-induced myoclonus in guinea pigs may be valuable in studying the organization of brainstem indoleamine systems that may be involved in some forms of human myoclonus.
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PMID:5-HT-mediated myoclonus in the guinea pig as a model of brainstem 5-HT and tryptamine receptor action. 241 49

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.
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PMID:Tryptamine-induced myoclonus in guinea-pigs pretreated with a monoamine oxidase inhibitor indicates pre- and post-synaptic actions of tryptamine upon central indoleamine systems. 613 Apr 89