The effects and after effects of the α2-adrenoceptor antagonist idazoxan on mood, memory and attention in normal volunteers

Abstract

Idazoxan, an α( 2)-adrenoceptor antagonist, is an effective antidepressant with a mode of action different from that of conventional antidepressants. As it is used as an antidepressant it is important to know whether there are any unwanted CNS side effects. Study of its effects will also provide information on the relationship between noradrenergic function and mood and performance. Twelve normal male volunteers who were given the drug (40 mg orally three times daily for 21 days) were compared with 12 matched controls. A computerized test battery was used to assess mood and various aspects of memory and attention. Many of the tests of memory and attention in the battery have been widely used over the last 20 years, and in addition two new selective attention tasks were included. The subjects were tested 3 days before starting the drug, on days 3 and 17 while on the drug, and after they had stopped taking the drug (4 days after and 24 days after). Control subjects followed a similar testing schedule. The results showed that the drug had no effect on mood, logical reasoning, retrieval from semantic memory or sustained attention. However, the drug did improve one aspect of selective attention (the place repetition effect), although this effect was only observed on the third day on the drug. Overall, the results suggest that idazoxan produces selective performance improvements, and that the measures of selective attention used here may be more sensitive indicators of drug effects than some of the traditional tasks currently in use.

Detection of visual signals by rats: effects of chlordiazepoxide and cholinergic and adrenergic drugs on sustained attention

“…3,4,5), an observation consistent with their recognized stimulant properties (Aghajanian et al 1977;Sara and Devauges 1989;Levin 1992;Smith et al 1992). In addition, changes in cognitive function induced by both nicotine (Levin 1992) and α 2 -adrenergic drugs (Arnsten and Goldman-Rakic 1985;Arnsten et al 1988) appear to involve inverted-U dose-effect relationships, a pattern consistent with the facilitation observed after 0.083 mg / kg and the disruption after 0.75 mg / kg of nicotine (Fig.…”

“…Thus treatment with the 2 -adrenergic agonist clonidine reduces noradrenergic activity (Starke et al 1974) and yields behavior consistent with reduced arousal (e.g., sedation and analgesia: Meyer et al 1977;Tilson et al 1977). Conversely, treatment with the 2 -adrenergic antagonist idazoxan tends to increase noradrenergic activity (Aghajanian et al 1977) and has been associated recently with improvements in memory (Sara and Devauges 1989) and attention (Devauges and Sara 1990;Smith et al 1992;Bunsey and Strupp 1995). These findings, as well as increased distractibility in the 5-CSRT task produced by lesions of the dorsal noradrenergic bundle (Carli et al 1983;Cole and Robbins 1992), led to the prediction that idazoxan will enhance, and clonidine impair, signal detection.…”

Effects of methylphenidate on spatial working memory and planning in healthy young adults

“…At higher doses in man, Coull et al (1995a) found some signiÞcant improvements in performance of CANTAB tests sensitive to frontal lobe dysfunction. Improvements in aspects of executive performance have also been found following administration of the a 2 -antagonist, idazoxan, which elevates functional noradrenaline levels (Smith et al 1992). Thus, there is evidence to suggest that noradrenaline also plays a role in frontal lobe function.…”

α2-Adrenoceptor antagonists potentiate acetylcholinesterase inhibitor effects on passive avoidance learning in the rat

“…Low, presynaptically active doses of clonidine may interfere with learning by reducing adrenergic activity (Arnsten and Goldman-Rakic 1985). Conversely, low but not high doses of ez-adrenoceptor antagonists such as yohimbine and idazoxan also appear to enhance memory retention and recall (Smith et al 1992). Sara and her co-workers showed improved recall of old memories of a linear maze task by rats tested immediately after administration of amphetamine and idazoxan (Sara and Devauges 1989;Devauges and Sara 1990).…”