Further extensions of the cosinor approach to problems of the pharmaceutical industry.

The resolution of a more complex time structure than that described by the useful first approximation of a single cosinor is suggested herein. The cosinor serves the purpose of parsimony in the case of sparse and short time series, yet it can be usefully extended by assessing the variations in rhythm characteristics for treatment timing in the clinic rather than only for research.

Differences in antiepileptic drug efficacy in hippocampally kindled normal and microcephalic rats.

The difference in antiepileptic drug efficacy was investigated in two groups of animals: 5 normal and 4 microcephalic rats. The latter were produced by a single i.p.

Effects of carbamazepine, AF-CX 921, and AF-CX 1325 on epileptic discharges and seizures in hippocampally kindled rats.

In nine hippocampally kindled rats (5 normal and 4 microcephalic) a comparative study of the antiepileptic effects of carbamazepine, and AF-CX 921 [(E)-2-[(alpha-amino)-phenylmethylene]-benzo-[b]-thiophene-3(2H)- one] and its metabolite AF-CX 1325 [(E)-2-[(alpha-amino)-phenylmethylene]-benzo-[b]-thiophene-3-(2H)- one-1-oxide], were compared with placebo. The treatment effects were tested 1, 2, 3, 4, and 5 h after drug administration, and the testings were executed twice for each treatment and animal. The following biological parameters were evaluated and statistically analyzed: duration of first AD (AD1); frequency of occurrence of focal spiking (FS) which followed AD1; frequency of occurrence of second AD (AD2) which followed FS; duration of total EEG epileptic activity (AD1 + FS + AD2); frequency of occurrence of convulsive seizures (CS); frequency of occurrence of partial seizures (epileptic behavior, automatisms); and frequency of occurrence of a quiet state of the animal, indicating no behavioral kindling response.

Interactions of brotizolam and diazepam with some psychotropic drugs on motor performance in mice.

The interaction of brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno [3,2-f]-1,2,4-triazolo[4,3-a]-1,4-diazepine, We 941, Lendormin) and diazepam with ethanol, phenobarbital, haloperidol and desipramine was investigated in a motor performance test (rotarod) in mice. Brotizolam and diazepam were tested at dose levels which partially impaired the motor performance. In combination with ethanol and phenobarbital only the anticipated additive effect was observed.