The effects of the novel anxiolytic drug lesopitron, a full and selective 5-HT1A receptor agonist, on pupil diameter and oral temperature in man: comparison with buspirone

We investigated the effects of two 5-HT1A receptor agonists, buspirone and lesopitron, upon pupil size in human volunteers at an ambient luminance lev el of 32 Cd m(-2) and in darkness. Pupil diameter was monitored with a bino cular infrared television pupillometer, before and after the administration of treatments for 4h at 20-min intervals. Two experiments were conducted. In Experiment 1, 14 healthy male volunteers participated in seven weekly se ssions, each associated with the ingestion of one capsule (buspirone 5, 10 and 20 mg, lesopitron 10, 20 and 40 mg and placebo), according to a double- blind balanced, cross-over design. Both buspirone and lesopitron tended to decrease pupil diameter. In darkness, only the highest dose of buspirone (2 0 mg) caused a miosis that was statistically significant. However, at the l uminance level of 32 Cd m(-2) buspirone 10 and 20 mg evoked statistically s ignificant miotic effects, as did the highest dose of lesopitron (40 mg). T he miotic effect was significantly greater at 32 Cd m(-2) than in darkness after each dose of buspirone and the highest dose (40 mg) of lesopitron. In Experiment 2, pupil diameter and oral temperature were monitored with an e lectronic thermometer at 40-min intervals. Twenty healthy male volunteers p articipated in two weekly sessions, each associated with the sublingual app lication of 100 mu l hydroalcoholic solution (lesopitron 20 mg, placebo), a ccording to a double-blind balanced cross-over design. Lesopitron caused a significant miosis both in darkness and at the luminance level of 32 Cd m(- 2); the miosis was greater at 32 Cd m(-2) than in darkness. Lesopitron tend ed to decrease oral temperature; this effect however, was not statisically significant. The greater effectiveness on the pupil of lesopitron administe red sublingually in a solution indicates the importance of first-pass metab olism in reducing the effectiveness of the drug when administered by the mo uth. The miosis observed in both experiments may be due to either a sympath olytic or a parasympathomimetic effect of the drugs, or both. The light-dep endence of the miosis indicates that the 5-HT1A receptor agonists can modul ate the light reflex, possibly via the noradrenergic control of central cho linergic neurones in the Edinger-Westphal nucleus.