Pharmacological and Behavioral Profile of Alpidem as an Anxiolytic

Abstract

Pharmacological and behavioral studies in mice and rats have shown that the imidazopyridine alpidem possesses anxiolytic activity with a profile which is substantially different from that of benzodiazepines. Thus, in mice, alpidem inhibited marble-burying behavior and enhanced feeding under stressful conditions, as did benzodiazepines; in contrast to these drugs, however, alpidem was inactive against shock-induced fighting and shock-suppressed exploration. In rats, alpidem exerted anticonflict activity in the punished drinking test, but failed to antagonize punishment-induced inhibition of operant behavior. Moreover, in rats trained to discriminate chlordiazepoxide from saline, alpidem did not produce a benzodiazepine-like interoceptive stimulus. Alpidem also produced anticonvulsant effects in a variety of tests sensitive to benzodiazepines. However, the order of potencies against convulsions induced by different convulsive agents was different from that of the benzodiazepines. Alpidem decreased motor performance in the rotarod test and only produced a deficit in muscle strength at doses which were more than 20 times higher than the doses active in anxiolytic tests. Moreover, alpidem did not interfere with the acquisition of conditioned fear, except at very high doses, indicating a weak potential to impair memory. The effects of alpidem were antagonized by flumazenil, indicating that central omega receptors are involved in the action of this drug. The weak sedative effects of alpidem may be attributed to its low intrinsic activity, as demonstrated by its low efficacy in increasing latency to isoniazid-induced convulsions.

Placebo-Controlled Sleep Laboratory Studies on the Acute Effects of Zolpidem on Objective and Subjective Sleep and Awakening Quality in Nonorganic Insomnia Related to Neurotic and Stress-Related Disorder

“…This led to the classification of alpidem as an anxiolytic and zolpidem as a sedative hypnotic, which was confirmed by pharmaco-EEG and sleep studies [48,49]. Zivkovic et al [50] also showed that these drugs were virtually devoid of muscle-relaxant activity and had a low potential to cause amnesia. Tolerance and physical dependence have been reported not to occur in animals [51] or humans [52].…”

Tratamento farmacológico do transtorno de ansiedade generalizada: perspectivas futuras

“…50 O alpidem, uma imidazopiridina com atividade seletiva nos receptores ω 1 , apresentou efeito ansiolítico em alguns modelos animais (esconder objetos e neofobia alimentar), mas não em outros modelos, exibindo, portanto, um perfil diferente dos BZD. 58 Em estudos clíni-cos, o alpidem apresentou efeito superior ao placebo em estudos clínicos, com início de ação já na primeira semana, e eficá-cia similar a dos BZD. 59 Em estudo aberto de longa duração (6-12 meses), não se observaram tolerância ao efeito ansiolítico do alpidem nem sintomas de abstinência na suspensão abrupta.…”

The pharmacological properties of Y‐23684, a benzodiazepine receptor partial agonist

“…One is BZR multiplicity, two receptor subtypes, BZ(omega), and BZ(omega)2, exist in different brain areas, subserving different physiological functions. The introduction of BZ,-selective imidazopyridines, zolpidem and alpidem (Depoortere et al, 1986;Zivkovic et al, 1990), has fuelled the debate about the functional consequences of receptor multiplicity (Doble & Martin, 1992). An alternative approach is the development of BZR partial agonists (Petersen, 1987;Muller, 1988;Haefely et al, 1990).…”