Imidazenil, a new anxiolytic and anticonvulsant drug, attenuates a benzodiazepine-induced cognition deficit in monkeys.
Imidazenil is a highly potent partial allosteric modulator of gamma-aminobutyric acid action at a great variety of gamma-aminobutyric acid(A) receptors, whereas alprazolam is a full allosteric modulator at these receptors. Data in rats indicate that imidazenil, like alprazolam, has pharmacological effects in animals indicative of anxiolytic, antipanic and anticonvulsant activity in humans, but unlike alprazolam, in animals imidazenil does not produce ataxia, sedation, tolerance or dependence nor does it potentiate the effects of ethanol. To extend the study of the imidazenil pharmacological profile, we administered this drug and alprazolam, alone and in combination, in monkeys working in a complex behavioral task. In one component of a multiple schedule (repeated acquisition or "learning"), patas monkeys acquired a different four-response chain each session by responding sequentially on three keys in the presence of four discriminative stimuli (geometric forms or numerals). In the other component (performance), the four-response chain was the same each session. The response chain in each component was maintained by food presentation under a fixed-ratio schedule. When alprazolam (0.01-0.32 mg/kg, p.o.) was administered alone, the overall response rate in both learning and performance decreased and the percent errors in both components increased with increasing doses. Learning, however, was more sensitive than performance; i.e., error-increasing effects were seen in learning at doses that had no effect on performance accuracy.(ABSTRACT TRUNCATED AT 250 WORDS)
Thompson
D M
DM
Center for Neuropharmacology, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, USA.
Auta
J
J
Guidotti
A
A
Costa
E
E
D000525:Alprazolam / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy*; D004901:Erythrocebus patas; D005260:Female; D018757:GABA Modulators / Q000627:therapeutic use; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D018757:GABA Modulators; D007093:Imidazoles; D001569:Benzodiazepines; C082661:imidazenil; D000525:Alprazolam