cinromide and Seizures

The effects of cinromide on two types of metrazol-induced seizures were studied in 236 male rats aged 7, 12, 18, 25 and 90 days. Cinromide was administered intraperitoneally in a dose of 25 or 50 mg.kg-1 30 min before a subcutaneous injection of metrazol. Major, i.e. generalized tonic-clonic seizures could be elicited by metrazol in all age groups. Cinromide was efficient against this type of seizures at all developmental stages, but its action in 7- and especially in 12-day-old rat pups was less marked than in older animals. Minimal metrazol seizures (predominantly clonic) could be reliably elicited since the age of 18 days. Cinromide was also able to suppress this type of seizures, but in adult rats the dose of 75 mg.kg-1 had to be administered because even the 50 mg.kg-1 dose was not sufficient. Quantitative changes of the antimetrazol action of cinromide were demonstrated during maturation in rats.

Topics: Aging; Animals; Anticonvulsants; Cinnamates; Male; Pentylenetetrazole; Rats; Rats, Inbred Strains; Seizures

The effect of the experimental anticonvulsant cinromide (3-bromo-N-ethylcinnamamide) on various inhibitory and excitatory mechanisms was investigated in the trigeminal nucleus of cats. Intravenous administration of 20-80 mg/kg cinromide depressed excitatory transmission and facilitated segmental inhibition to the same extent as phenytoin, but less than carbamazepine. These doses of cinromide also depressed periventricular inhibition, similar to valproate and ethosuximide. In addition, cinromide had a marked depressant effect on the EEG, suggesting a pronounced sedative effect. The serum levels of cinromide and of its active metabolites (3-bromocinnamamide and 3-bromocinnamic acid) were comparable to those in patients receiving long-term treatment with cinromide. Our results agree with those in other experimental models, which also suggest that cinromide is a broad-spectrum anticonvulsant, and with cinromide's effect in the clinical trials reported so far.

Topics: Animals; Cats; Cinnamates; Seizures; Synaptic Transmission; Trigeminal Nuclei

Cinromide, an experimental anticonvulsant (Burroughs Wellcome Co.) was tested against focal cortical (simple partial analog), focal amygdala (complex partial analog), and generalized convulsive (tonic-clonic analog) seizures in the "kindled" rat. The toxicity in the CNS was measured by the ataxia scale devised by Desmedt, Niemegeers, Lewi and Janssen (Arzneimittel-Forsch, 26: 1592-1602, 1976). Cinromide was found to suppress generalized convulsions in small, subtoxic doses, whereas larger, sometimes toxic doses were required to suppress focal seizure activity. The general pattern of response resembles that of the standard clinical anticonvulsants which the present authors have previously investigated. Cinromide, however, was relatively more potent against focal amygdala (complex partial analog) seizures than any drug previously tested, except carbamazepine. These data suggest that cinromide should be clinically effective, not only against tonic-clonic seizures, but also, toxicity permitting, against complex partial attacks as well.

Topics: Animals; Anticonvulsants; Cinnamates; Kindling, Neurologic; Male; Rats; Rats, Inbred Strains; Seizures

In a previous study (Lockard et al., 1979) Cinromide (3 bromo-N-ethylcinnamamide), an experimental anticonvulsant (Burroughs-Wellcome Pharmaceutical Co.), was given a preliminary evaluation. Since that research was concerned primarily with EEG paroxysms, the present study was conducted to address drug efficacy in terms of clinical seizures. Cinromide's major metabolite (3-bromocinnamamide, BC) was the main focus. Eight alumina-gel monkeys were given by gastric bolus every 6 hr for 10 days (Phase I) either the solvent alone (Tween 80), Cinromide (BEC), or its synthetic metabolite (SBC). Subsequently (Phase II), four animals were given BEC or SBC by chronic gastric infusion for 20 days. In both phases Cinromide's metabolite (either via BEC or especially SBC) was effective in half of the animals in reducing seizure frequency and/or duration at plasma levels above 5 mcg/m. The data suggest that the drug's efficacy is individually specific. Another species of Cinromide metabolism, 3-bromocinnamic acid, is also discussed.

Topics: Animals; Anticonvulsants; Cinnamates; Electroencephalography; Haplorhini; Macaca mulatta; Male; Seizures; Stomach