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

Fluoxetine is a bicyclic antidepressant that is a specific and potent inhibitor of the presynaptic reuptake of serotonin. It has essentially no effect on the reuptake of norepinephrine or other neurotransmitters. Similarly, it has negligible binding affinity for neurotransmitter receptor sites. It is well absorbed after oral administration, with absolute bioavailability in dogs of approximately 72 +/- 27.6%. The mean Tmax is between 4 and 8 hours, and it is approximately 94% protein bound. After a single dose, the elimination half-life is 1-3 days. After long-term administration, the elimination half-life averages 4 days. Its pharmacokinetics appear nonlinear. It is metabolized to an active metabolite norfluoxetine, which is also specific for the inhibition of serotonin reuptake. Norfluoxetine's elimination half-life averaged 7 days after long-term administration. Little is known about potential drug interactions; however, fluoxetine appears to have minimal clinically relevant interactions. Fluoxetine is indicated in the treatment of major depression. Its efficacy is comparable to the tricyclics and it has a similar onset of action. Although doses as high as 80 mg/day have been used, the optimal dosage range appears to be 20-40 mg once daily. Fluoxetine has been used with success in obsessive-compulsive disorder and intention myoclonus, however, its use in these disorders remains investigational. The frequency of side effects is low and dose related; the most common effects are nausea, anxiety, insomnia, anorexia, diarrhea, nervousness, and headache. Eight reports of intentional overdose with fluoxetine alone resulted in no deaths and mild adverse effects. It will be marketed as 20-mg capsules under the brand name of Prozac. Although fluoxetine should be added to formularies, its use should be reserved for treatment of those who do not respond to or do not tolerate tricyclic agents.
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PMID:Fluoxetine: a serotonin-specific, second-generation antidepressant. 355 56

We review the neurochemical and behavioral profile of the selective gamma-aminobutyric acid (GABA) uptake inhibitor, (R)-N-(4,4-di-(3-methylthien-2-yl)but-3-enyl) nipecotic acid hydrochloride [tiagabine (TGB), previously termed NNC 05-0328, NO 05-0328, and NO-328], which is currently in phase III clinical trials for epilepsy. TGB is a potent, and specific GABA uptake inhibitor. TGB lacks significant affinity for other neurotransmitter receptor binding sites and/or uptake sites. In electrophysiological experiments in hippocampal slices in culture, TGB prolonged the inhibitory postsynaptic potentials (IPSP) and inhibitory postsynaptic currents (IPSC) in the CA1 and CA3 produced by the addition of exogenous GABA. In vivo microdialysis shows that TGB also increases extracellular GABA overflow in a dose-dependent manner. Together these biochemical data suggest that the in vitro and in vivo mechanism of action of TGB is to inhibit GABA uptake specifically, resulting in an increase in GABAergic mediated inhibition in the brain. TGB is a potent anticonvulsant agent against methyl-6,7-dimethyoxy-4-ethyl-B-carboline-3-carboxylate (DMCM)-induced clonic convulsions (mice), subcutaneous pentylenetetrazol (PTZ)-induced tonic convulsions (mice and rats), sound-induced convulsions in DBA/2 mice and genetically epilepsy-prone rats (GEPR), and electrically induced convulsions in kindled rats. TGB is partially efficacious, against subcutaneous PTZ-induced clonic convulsions, and photically induced myoclonus in Papio papio. TGB is weakly efficacious in the intravenous PTZ seizure threshold test and the maximal electroshock seizure (MES) test and produces only partial protection against bicuculline (BIC)-induced convulsions in rats. The overall biochemical and anticonvulsant profile of TGB suggests potential utility in the treatment of chronic seizure disorders such as generalized clonic-tonic epilepsy (GTCS), photomyoclonic seizures, myoclonic petit mal epilepsy, and complex partial epilepsy.
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PMID:A review of the preclinical pharmacology of tiagabine: a potent and selective anticonvulsant GABA uptake inhibitor. 755 76