A fragment was obtained by treating Clostridium perfringens enterotoxin with 2-nitro-5-thiocyanobenzoic acid, a reagent which specifically cleaves the amino-terminal peptide bond of cysteine residues. The fragment (molecular weight, 15,000) was purified by high-performance liquid chromatography. The fragment had no cytotoxic effect on Vero cells but competitively inhibited enterotoxin-induced 51Cr release. Binding of

ABSTRACT-~-Carboline abecarnil was behaviorally and biochemically characterized as a new anxiolytic agent in rodents and primates in comparison with the benzodiazepine (BZ) anxiolytics. Oral treatment with abecarnil (0.5 10 mg/kg) showed a potent anticonflict activity in the water-lick test in rats. The minimal effective dose was lower than those of BZ anxiolytics, such as etizolam, diazepam, clotiazepam and tofisopam. Abecarnil also showed taming effects to suppress fighting and aggressive behaviors in mice and monkeys with little sedative and ataxic effects, in contrast to the BZ anxiolytics producing marked sedative and ataxic effects. Furthermore, abecarnil suppressed both the sedative and ataxic effects induced by diazepam. Abecarnil bound to rat cerebellar BZ1 receptors (Ki=0.24 nM) with a higher affinity than to rat spinal cord BZ2 receptors (Ki=1.3 nM), whereas BZ derivatives bound to both the receptors with a low and equal affinity. GABA-ratios of abecarnil were 1.9 for the BZ, receptors and 2.8 for the BZ2 receptors, and they were smaller than those of diazepam and flunitrazepam. Thus, in contrast to the BZ derivatives, abecar nil may act as a selective partial agonist at central BZ, receptors, resulting in its potent anticonflict and tam ing effects with little sedative and ataxic effects.

ABSTRACT-To clarify the roles of dopamine D, and D2 receptors in behavioral symptoms of Parkinson's disease, antiparkinsonian effects of various dopamine agonists in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian monkeys were investigated with regard to induction of hyperactivity such as excitability, irritability and aggressiveness. The non-selective dopamine agonist apomorphine ameliorated the parkinsonism, but induced marked hyperactivity dose-dependently. Pretreatment with either the dopamine D, antagonist SCH 23390 or the dopamine D2 antagonist sulpiride markedly suppressed the apomorphine-induced hyperactivity with slight attenuation of the antiparkinsonian effects. Both the dopamine D2-receptor agonist quinpirole and the dopamine D,-receptor agonist SKF 82958 ameliorated the parkinsonism in a dose-dependent manner with a slight induction of hyperactivity. Combination treatment of a threshold dose of quinpirole with that of SKF 82958 augmented the antiparkinsonian effects without a marked induction of hyperactivity. However, the combination treatment at higher doses induced marked hyperactivity accompanied by augmented antiparkinsonian effects. These results suggest that stimulation of either central dopamine D, or D2 receptors is requisite for the antiparkinsonian effects and concurrent strong stimulation of both central dopamine D, and D2 receptors causes marked hyperactivity which may be predictive of dopaminergic psychiatric side effects.

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