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

Stereotaxic injections of a dopamine D1 receptor agonist (SKF 38393) into different regions of the supersensitive striatum of rats with a unilateral 6-hydroxydopamine-induced lesion duplicated the systemic effects of the drug in a topographical manner. Although there was considerable overlap, it was possible to recognize discrete active zones or "hot-spots" giving rise to prominent sniffing, head movements and contralaterally directed circling, posture and grooming, both in the coronal plane and along the rostro-caudal axis. Two behaviours peculiar to D1 stimulation included contralateral forepaw myoclonus and forepaw nibbling, which paradoxically was directed mainly ipsilaterally. Each of the behavioural elements occurred independently of the others and after an inexplicably long latency. They were inhibited by the D1 antagonist SCH 23390, but not by the D2 blocking drug metoclopramide. Comparable circling responses were evoked by a D2 agonist (lisuride) injected into the neostriatum after a short delay, and instantaneously by apomorphine (D1/D2 agonist). Both drug behaviours originated diffusely from all parts of the denervated striatum with no obvious "hot-spots", except for circling which exhibited a bimodal distribution rostro-caudally. The actions of lisuride were blocked by systemic metoclopramide, but not by SCH 23390, while the actions of apomorphine were inhibited by both antagonists. Topographies of D2 receptor-mediated events were quite different from those encountered for D1 receptor stimulation by SKF 38393, though neither corresponded to the autoradiographic distribution of D1 and D2 binding sites in the intact striatum. These results reiterate the importance of D1 receptors in motor control and provide a basis for future investigations of the output pathways subserving D1-mediated behaviours.
 ...
PMID:Topography of dopamine behaviours mediated by D1 and D2 receptors revealed by intrastriatal injection of SKF 38393, lisuride and apomorphine in rats with a unilateral 6-hydroxydopamine-induced lesion. 295 90

Effects of SK&F 83822 [3-allyl-6-chloro-7,8-dihydroxy-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine], an agonist at dopamine D1-like receptors which stimulate adenylyl cyclase but not phosphoinositide hydrolysis, were studied topographically so as to clarify differences between these receptors in the regulation of behaviour. Using cloned receptors, SK&F 83822 showed high, selective affinity for dopamine D1 and D5 over D2, D3, D4 and several non-dopamine receptors. SK&F 83822 induced little intense grooming, but readily induced sniffing, locomotion and rearing; seizures were evident at higher doses, characterised by tonic convulsions, forepaw myoclonus and explosive hyperlocomotion. The dopamine D1-like receptor antagonist SCH 23390 [R(+)-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine] readily antagonised these responses to SK&F 83822, particularly seizure activity. The dopamine D2-like receptor antagonist YM 09151-2 [cis-N-(1-benzyl-2-methyl-pyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylaminobenzamide] did not alleviate seizures induced by SK&F 83822; YM 09151-02 did, however, attenuate SK&F 83822-induced sniffing, locomotion and rearing, and released vacuous chewing. These findings indicate that dopamine D1-like receptors linked to adenylyl cyclase can be differentiated from those not linked to adenylyl cyclase in terms of their roles in the topographical regulation of behaviour. For example, the seizure and vacuous chewing responses appear to involve dopamine D1-like receptors that stimulate adenylyl cyclase, while intense grooming involves those which do not.
 ...
PMID:SK&F 83822 distinguishes adenylyl cyclase from phospholipase C-coupled dopamine D1-like receptors: behavioural topography. 1498 49