Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In cats, tremor produced by intraperitoneal pentobarbitone sodium or by intramuscular chlorpromazine was abolished by injection into the cerebral ventricles of a few gamma of adrenaline or noradrenaline, but not of other sympathomimetic amines or of anti-Parkinsonian drugs. Chloralose, urethane, calcium chloride, and magnesium chloride produced anti-tremor activity when administered in this way. When adrenaline or noradrenaline was perfused from a lateral ventricle to the aqueduct during pentobarbitone sodium tremor, tremor was inhibited when less than 1 mug. had been perfused. Adrenaline was at least four times as active as noradrenaline. Isoprenaline inhibited tremor when perfused in higher concentrations, but perfusion of ephedrine, amphetamine or of the anti-Parkinsonian drugs in high concentrations was ineffective. Perfusion of 2 mug. of chloralose or of 20 mug. of calcium chloride was sufficient to inhibit tremor. Intraventricular injections of 250 to 500 mug. of 5-hydroxytryptamine initiated tremor. Possible physiological implications of these findings are discussed.
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PMID:Tremor in cats: the effect of administration of drugs into the cerebral ventricles. 1910 41

Parkinson's disease (PD) is characterized by progressive loss of midbrain dopaminergic neurons and treated with the dopamine precursor, 3,4-dihydroxy-l-phenylalanine (L-DOPA). Prolonged L-DOPA treatment is however associated with waning efficacy and the induction of L-DOPA induced dyskinesia (LID). GPR88 is an orphan G-protein Coupled Receptor (GPCR) expressed in dopaminoceptive striatal medium spiny neurons (MSNs) and their afferent corticostriatal glutamatergic neurons. Here, we studied the role of GPR88 in experimental parkinsonism and LID. Chronic L-DOPA administration to male GPR88 KO mice, subjected to unilateral 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle, resulted in more rotations than in their WT counterparts. Conversely, GPR88 KO mice had a lower abnormal involuntary movements (AIMs) score. These behavioral responses were accompanied by altered transcription of L-DOPA upregulated genes in lesioned GPR88 KO compared to WT striata. In accordance with a role for serotonin neurons in LID development, WT but not GPR88 KO striata exhibited 5-hydroxytryptamine displacement upon repeated L-DOPA treatment. Intact male GPR88 KO mice showed diminished tacrine-induced PD-like tremor and spontaneous hyperlocomotion. Dopamine and its metabolites were not increased in male GPR88 KO mice, but biosensor recordings revealed increased spontaneous/basal and evoked glutamate release in striata of male GPR88 KO mice. In conclusion, genetic deletion of GPR88 promotes l-DOPA-induced rotation and spontaneous locomotion yet suppresses the induction of LIDs and also reduces tremor. These data provide behavioral, neurochemical and molecular support that GPR88 antagonism may favour motor relief in PD patients without aggravating the induction of motor side effects.
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PMID:Genetic deletion of GPR88 enhances the locomotor response to L-DOPA in experimental parkinsonism while counteracting the induction of dyskinesia. 3166 99


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