Discriminative stimulus properties of pentylenetetrazol and bemegride: some generalization and antagonism tests.

In an operant procedure of lever pressing on a FR 10 schedule of food reinforcement, male hooded rats were trained to respond with a lever on one side of a food cup following a drug injection, and to respond with a lever on the alternate side following a 1 ml/kg saline injection. All of 14 subjects learned to discriminate reliably between the effects of 20 mg/kg pentylenetetrazol (PTZ) and saline. Seven of eight rats learned to discriminate between the effects of bemegride (5 mg/kg) and saline. None of 14 rats learned to discriminate between 5mg/kg PTZ and saline. The bemegride discriminative stimulus generalized to PTZ (20mg/kg) and was antagonized by chlordiazepoxide (10 mg/kg). Chlordiazepoxide, diazepam, flurazepam, clobazam, and meprobamate were all effective antagonist of PTZ in a dose-dependent manner. Bemegride and cocaine generalized to the PTZ discriminative stimulus in a dose-dependent manner, but d-amphetamine, methylphenidate, and nicotine did not. Since bemegride and PTZ are convulsants at higher doses, the discriminative stimulus properties of these drugs might be based on a subtle convulsive brain state. The anxiolytic properties of benzodiazepines and meprobamate suggest that the discriminative stimulus produced by these convulsants is related to an "anxiety-inducing" action.

The synthesis and pharmacology of a novel benzodiazepine derivative, 1-(beta-methylsulfonylethyl)-5-(o-fluorophenyl)-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-one (ID-622).

The pharmacological profiles of a new benzodiazepine derivative, 1-(beta-methylsulfonylethyl)-5-(o-fluorophenyl)-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-one (ID-622), were shown. In anti-convulsant test, ID-622 was more potent than diazepam and medazepam when tested with pentylenetetrazol or bemegride, but was less potent than diazepam tested with strychnine or MES in mice. Taming effects of ID-622 were more potent than diazepam in both electroshock- and isolation-induced fighting mice tests, but were less potent in both septal rats and O.B. rats tests. ID-622 had only a weak influence on the spontaneous locomotor activity, and did not cause the righting reflex loss. In EEG, ID-622 increased fast activity and depressed hippocampal I-waves and amygdala after-discharge in cats. Acute toxicity of ID-622 was very low.