Stereospecificity of behavioural effects of viloxazine in bulbectomized rats does not correlate with its 5-HT-releasing action in vitro

Abstract

The effects of the antidepressant drug viloxazine and its two optically active isomers on the passive avoidance learning deficit surgically induced in rats by bilateral bulbectomy have been determined. Fourteen consecutive daily injections of either the racemate or the S-isomer (2, 5 and 10 mg kg-1 i.p.) significantly improved the acquisition of avoidance behaviour. The R-isomer was devoid of such activity in this same dose range. The various isomeric species of viloxazine were also studied in vitro for their ability to induce a release of noradrenaline, dopamine and 5-hydroxytryptamine (5-HT) from rat brain slices. In agreement with previous reports, racemic viloxazine caused a concentration-dependent (10(-5)-10(-3 M) release of 5-MT without affecting any significant change in the release of either catecholamine. However, in contrast to the results of the behavioural studies, this phenomenon did not exhibit stereospecificity, all three isomeric forms being equally active. Thus, there is no simple relationship between viloxazine's behavioural activity in bulbectomized rats and its 5-HT releasing properties observed in vitro. The significance of these findings with respect to previously reported effects of the drug indicative of facilitation of central 5-HT mediated processes is discussed.

An Open Field Study of Antidepressant Drugs

“…Viloxazine (2-(2-ethoxyphenoxymethyl)-tetrahydro-1,4-oxazine) is a second generation monocyclic antidepressant agent with a profile different from the tricyclics (Lippmann & Pugsley 1976;Pinder et al 1977). Viloxazine does not interfere with the dopamine system but inhibits NA reuptake (Greenwood 1975), and releases serotonin (Greenwood et al 1982). It has a stimulatory clinical profile (Blackwell 1987).…”