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)

The hypothesis that central neurotransmitter receptor abnormalities are the basis of human myoclonic disorders is novel. Receptor abnormalities in any of several different neurotransmitter systems implicated in myoclonus may be genetic or the consequence of various brain injuries. These abnormalities might define pharmacologic subgroups of possible relevance to the clinical, neurophysiologic, and pathologic heterogeneity of myoclonus. Receptor abnormalities may be the primary pathophysiologic defect, involving the surface recognition site or effector-transducer mechanisms in the defect, involving the surface recognition site or effector-transducer mechanisms in the post-synaptic cell. Alternatively, changes in receptor density or affinity may be adaptive (recovery of function) or maladaptive (supersensitivity, subsensitivity, dysregulation). Drug treatments, then, could be targeted at the receptor changes, reversing abnormalities and enhancing compensatory mechanisms. Current therapy may inadvertently have such an effect. Polytherapy may be justified to target more than one component of the "pharmacologic receptor". Identification of receptor abnormalities in human post-mortem brain may have diagnostic and therapeutic significance. New advances in the pharmacologic selectivity of receptor agonists and antagonists and in the measurement of receptors should be applied to the problem of myoclonus.
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PMID:The proposed role of neurotransmitter receptors in the pathophysiology of human myoclonic disorders. 257 16

There have been few previous studies of the functional significance of 5,7-dihydroxytryptamine (5,7-DHT) lesions made in neonatal rats. To study the role of serotonin (5-HT) in recovery of function, rat pups and adult rats were injected intracisternally with 5,7-DHT or saline and challenged acutely with the 5-HT precursor 5-hydroxytryptophan (5-HTP) 4 weeks later as a test of behavioral supersensitivity. Compared to 5,7-DHT lesions in adults, neonatal lesions induced significantly greater 5-HT depletions in brainstem, but 5-HT depletions in other regions were not significantly different in the two groups. Rats with early 5,7-DHT lesions displayed supersensitive behavioral responses to 5-HTP, consisting of all the component myoclonic-serotonergic behaviors seen in rats with 5,7-DHT lesions made as adults. However, there was significantly less 5-HTP-evoked head weaving, truncal myoclonus and shaking behavior in rats treated with 5,7-DHT as neonates. Body weight was reduced both in rats with early and late 5,7-DHT lesions, but reduction persisted in rats with early lesions. These data indicate overall similarity with some differences between neurochemical and behavioral effects of early and late 5,7-DHT lesions made by the intracisternal route. They suggest that recovery mechanisms did not occur or failed to reverse the neurochemical or behavioral consequences of early 5,7-DHT lesions.
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PMID:Intracisternal 5,7-dihydroxytryptamine lesions in neonatal and adult rats: comparison of response to 5-hydroxytryptophan. 278 68