Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anticonvulsant effects of four benzhydryl piperazines, SC-13504 (ropizine, an anticonvulsant), hydroxyzine (HDX, an anxiolytic), chlorcyclizine (CCZ, an antihistaminic) and buclizine (BUC, an antihistaminic), were investigated utilizing a modified maximal electroshock seizure test in rats. In addition to detecting the presence or absence of tonic hindlimb extension, the modified method quantified various phases of the seizure. All four benzhydryl piperazines exhibited anticonvulsant activity in maximal electroshock seizure, but SC-13504 was similar in efficacy to phenobarbital and phenytoin, and much more effective than HDX, CCZ or BUC. Additionally, SC-13504 possessed a therapeutic index much greater than any of the compounds tested. The duration of action of the benzhydryl piperazines, in hours was: SC-13504, 0.5 to 8; HDX, 0.5 to 2; CCZ, 0.5 to 16; and BUC, 2 to 8. Buc and CCZ are postulated to be converted to active anticonvulsant metabolites.
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PMID:Anticonvulsant effects of benzhydryl piperazines on maximal electroshock seizures in rats. 3 12

Studies were conducted on a colony of purebred beagle dogs. Animals with spontaneous seizures were classed as epileptic beagles (EB). Those without spontaneous seizures were termed nonepileptic beagles (NEB). The median convulsant current for maximal electroshock seizure (MES) threshold was 175(194-158)mA for EB and 390 (417-364) mA for NEB. Similarly the median convulsant dose of pentylenetetrazol (PTZ) was 7.9 (10.1-6.2) mg/kg for EB and 20.2 (24.2-17.6) mg/kg for NEB. Following pretreatment with graded doses of ropizine (SC 13504), the median protective dose against MES was 6.0(9.2-3.9) mg/kg in EB and 3.2(4.8-2.1) mg/kg in NEB. Based on the incidence of ataxia, EB had a median toxic dose (TD50) of 14.0(16.5-11.9) mg/kg, while in NEB it was 18.0(23.6-13.7)mg/kg. The TD50 doses were unable to protect against a convulsive dose of PTZ. It is concluded first that ropizine may have anti-grand mal activity but apparently lacks an anti-petit mal action. Secondly, EB are more sensitive than NEB to the convulsive effects of electric current and PTZ, yet less responsive to the anticonvulsant actions of ropizine.
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PMID:Anticonvulsant properties of ropizine in epileptic and nonepileptic beagle dogs. 63 71

The status of Papio papio as a model of clinical epilepsy has been reviewed. The anticonvulsant effects of single doses of various classic and experimental agents have been compared against seizures induced in the P. papio by intermittent light stimulation. Long-acting but not short-acting barbiturates have been shown fully to control seizures with minor sedative effects. Diphenylhydantoin (in chronic doses only) and trimethadione are often effective but not consistently so. Diazepam and clonazepam block seizures at very low doses both acutely and chronically. However, an initial dose well above threshold seems essential if anticonvulsant effects are to be maintained under chronic administration of these compounds. Carbamazepine and SC 13504 (1-benzhydryl-4(6 methyl-2-pyridylmethyleneimino)piperazine), as well as two nonstimulant analogues of amphetamine, were shown to be promising anticonvulsants in this model. A biphasic action of tetrahydrocannabinol, anticonvulsant at a few micrograms per kilogram but not at higher doses, was also demonstrated. Finally, the anticonvulsant action of intraventricular epinephrine and norepinephrine was reported.
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PMID:Measurement of anticonvulsant activity in the Papio papio model of epilepsy. 82 87

SC-13504 was given intravenously to baboons with photosensitive epilepsy, Papio papio, with and without prior administration of allylglycine. Plasma levels of the drug were determined by differential pulse polarography and correlated with behavioural changes and the anticonvulsant action of the drug. Protection against photically induced seizures or self-sustaining myoclonic responses was seen 30 to 120 min after SC-13504, 4-8 mg/kg (when plasma levels were 1 mug/ml or greater). EEG and neurological signs of toxicity were seen after SC-13504 8 mg/kg but not after 4-6 mg/kg.
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PMID:The relationship between the anticonvulsant properties of SC-13504 and its plasma levels, measured by polarography, in baboons with photosensitive epilepsy. 82 76