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 effect of two drugs upon multifocal myoclonic jerks was evaluated. The drugs influence the central cholinergic system in opposite ways. Eight patients with progressive and nonprogressive myoclonic epilepsy were tested. The single blind test was used. The number of myoclonic jerks after intravenous physostigmine (mean dose 0.02 mg/kg) and that after atropine (0.04 mg/kg) was compared to number of myoclonic jerks in the drug-free periods and with placebo. Placebo was without an effect. Physostigmine slightly increased the number of jerks. Atropine decreased the number significantly. In most patients the results were not striking. It is suggested that the cholinergic system may participate in the physiopathology of the studied myoclonus in a rather indirect, perhaps modulating way.
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PMID:Influence of cholinergic system on myoclonus in myoclonic epilepsies. 162 Jan 39

Behavioral responses to atropine in rats exposed to the potent anticholinesterase agents Soman and Sarin were studied. Atropine itself produced limb-shakes and certain stereotyped activities, in a dose-dependent manner. The neurotoxicity elicited by Soman and Sarin was antagonized by atropine, while at the same time the responses induced by the latter were attenuated. In contrast, where rats were challenged with atropine 6-72 h after giving single doses of Soman or Sarin, the limb-shake myoclonus was markedly enhanced. The atropine-induced stereotypies were not, however, significantly affected, except for an increase seen at 24 h after Sarin treatment. Repeated treatment with Soman for 3 wk also led to similar supersensitivity of atropine-induced responses. The peripheral muscarinic receptor antagonist, methylatropine, produced no such hyperactivity on its own or at any time after anticholinesterase exposure. The rapid occurrence of hypersensitivity to antimuscarinic compounds following exposure to these anticholinesterases, therefore, suggests the need for observation of subjects who are poisoned with such agents and treated with antimuscarinics, for adverse reactions such as myoclonus during the critically sensitive period, especially if repeated antimuscarinic therapy is carried out.
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PMID:Hypersensitivity to antimuscarinic agents following brief exposure to Soman and Sarin. 370 76

Rats injected intrastriatally with picrotoxin and carbachol showed sustained myoclonic jerks of the contralateral forelimb. The role of acetylcholine and dopamine in picrotoxin myoclonus was examined by measuring the effects of intrastriatal pharmacological agents on the frequency and intensity of the jerks. Atropine and hemicholinium-3, which reduce acetylcholine function, antagonized the myoclonus. Apomorphine, which has been shown to reduce striatal dopamine function via "autoreceptors", potentiated the jerking, whereas D-amphetamine antagonized the myoclonus. The findings are discussed in relation to proposed interconnections of striatal neurones.
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PMID:Role of acetylcholine and dopamine in myoclonus induced by intrastriatal picrotoxin. 707 34

Huperzine A (HupA) is a naturally occurring compound found in the firmoss Huperzia serrata. While HupA is a potent acetylcholinesterase inhibitor, its full pharmacologic profile is incompletely described. Since previous works suggested a capacity for HupA to prophylax against seizures, we tested the HupA antiepileptic potential in pentylenetetrazole (PTZ) rat epilepsy model and explored its mechanism of action by spectral EEG analysis and by paired-pulse transcranial magnetic stimulation (ppTMS), a measure of GABA-mediated intracortical inhibition. We tested whether HupA suppresses seizures in the rat PTZ acute seizure model, and quantified latency to first myoclonus and to generalized tonic-clonic seizure, and spike frequency on EEG. Additionally, we measured power in the EEG gamma frequency band which is associated with GABAergic cortical interneuron activation. Then, as a step toward further examining the HupA antiepileptic mechanism of action, we tested long-interval intracortical inhibition (LICI) using ppTMS coupled with electromyography to assess whether HupA augments GABA-mediated paired-pulse inhibition of the motor evoked potential. We also tested whether the HupA effect on paired-pulse inhibition was central or peripheral by comparison of outcomes following administration of HupA or the peripheral acetylcholinesterase inhibitor pyridostigmine. We also tested whether the HupA effect was dependent on central muscarinic or GABAA receptors by co-administration of HupA and atropine or PTZ, respectively. In tests of antiepileptic potential, HupA suppressed seizures and epileptic spikes on EEG. Spectral EEG analysis also revealed enhanced gamma frequency band power with HupA treatment. By ppTMS we found that HupA increases intracortical inhibition and blocks PTZ-induced cortical excitation. Atropine co-administration with HupA did not alter HupA-induced intracortical inhibition suggesting independent of muscarinic acetylcholine receptors mechanism in this model. Last, pyridostigmine did not affect the ppTMS-measured cortical inhibition suggesting that HupA-induced effect is centrally-mediated. Our data support antiepileptic HupA applications, and suggest that such activity may be via enhancement of GABAergic intracortical inhibition.
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PMID:Huperzine A prophylaxis against pentylenetetrazole-induced seizures in rats is associated with increased cortical inhibition. 2643 30