Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0233565 (bradykinesia)
 2,352 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate the nigrostriatal involvement in rubral tremor, we studied single photon emission computed tomography (SPECT) imaging with [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]oct-2- yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)- N2,N2',S2,S2']oxo-[1R-(exo-exo)]-[99mTc]technetium ([99mTc]TRODAT-1) in a 70-year-old woman with a midbrain hemangioma. She had developed a slow tremor in her right arm and leg after an episode of hemorrhage at the age of 28. The tremor was 3 to 5 Hz in frequency at rest, which was enhanced by outstretching the limb and action. There was no rigidity or bradykinesia. Neurological examination also revealed mild palsy of the left oculomotor nerve. The magnetic resonance imaging (MRI) of the brain showed a small hemangioma in the left midbrain localized mainly in the substantia nigra. The [99mTc]TRODAT-1 SPECT imaging revealed significantly reduced [99mTc]TRODAT-1 uptake in the left caudate and putamen, but it was only mildly reduced in the right striatum. This reduction in uptake was even more severe than that of patients with Parkinson's disease, and indicated that the dopamine function was markedly impaired in the left nigrostriatal system. The tremor had not progressed over the years, and she responded moderately to treatment with levodopa. We concluded that the rubral tremor in the right extremities was probably caused by a dopamine deficiency in the left nigrostriatal system. This suggests that a dopamine deficiency secondary to the midbrain hemangioma might have contributed to the development of the rubral tremor in this patient.
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PMID:Dopamine deficiency in rubral tremor caused by midbrain hemangioma: case report. 1103 51

These studies evaluated the potential antiparkinsonian properties of the novel dopamine D(3)/D(2) receptor agonist S32504 [(+)-trans-3,4,4a,5,6, 10b-hexahydro-9-carbamoyl-4-propyl-2H-naphth[1,2-b]-1,4-oxazine] in comparison with those of the clinically employed agonist ropinirole. In rats with a unilateral, 6-hydroxydopamine lesion of the substantia nigra, S32504 (0.0025-0.04 mg/kg, s.c.) more potently elicited contralateral rotation than S32601 [(-)-trans-3,4,4a,5,6, 10b-hexahydro-9-carbamoyl-4-propyl-2H-naphth-[1,2-b]-1,4-oxazine (its less active enantiomer)], ropinirole, and l-3,4-dihydroxyphenylalanine (l-DOPA). Rotation elicited by S32504 was blocked by the D(2)/D(3) receptor antagonists haloperidol and raclopride and by the D(2) antagonist L741,626 [4-(4-chlorophenyl)-1-(1H-indol-3-ylmethyl)piperidin-4-ol], but not by the D(3) antagonist S33084 [(3aR,9bS)-N-[4-(8-cyano-1,3a,4,9b-tetrahydro-3H-benzopyrano[3,4-c]pyrrole-2-yl)-butyl]-(4-phenyl)benzamide]. As assessed by dialysis in both lesioned and nonlesioned animals, S32504 (0.04-2.5 mg/kg, s.c.) reduced striatal levels of acetylcholine. This effect was blocked by raclopride, haloperidol, and L741,626 but not S33084. In rats treated with reserpine, hypolocomotion was reversed by S32504 and, less potently, by ropinirole. In "unprimed" marmosets treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, both s.c. (0.01-0.04 mg/kg) and p.o. (0.04-1.25 mg/kg) administration of S32504 dose-dependently and rapidly (within 10 min) increased locomotor activity and reduced disability. Furthermore, S32504 dose-dependently reversed bradykinesia and improved posture in "L-DOPA-primed" animals, whereas eliciting less pronounced dyskinesia than l-DOPA. Finally, in terminally differentiated SH-SY5Y cells presenting a dopaminergic phenotype, S32504, but not S32601, abrogated the neurotoxic effects of 1-methyl-4-phenylpyridinium, an action inhibited by raclopride and S33084 but not L741,626. Ropinirole was weakly neuroprotective in this model. In conclusion, S32504 displays potent and stereospecific activity in rodent, primate, and cellular models of antiparkinsonian properties. Although activation of D(2) receptors is crucial to the motor actions of S32504, engagement of D(3) receptors contributes to its neuroprotective properties.
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PMID:S32504, a novel naphtoxazine agonist at dopamine D3/D2 receptors: II. Actions in rodent, primate, and cellular models of antiparkinsonian activity in comparison to ropinirole. 1497 95