Disease relevance of Lesopitron

• 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 [1].
• The acute toxicity of lesopitron is low and it does not potentiate the effects of alcohol or barbiturates [2].

Psychiatry related information on Lesopitron

• Establishing the maximum tolerated dose of lesopitron in patients with generalized anxiety disorder: a bridging study [3].
• Lesopitron has negligible effects on alpha-adrenergic and dopaminergic receptors [162653], and was more potent than structurally-related 5-HT1A agonists in rat social interaction and marmoset anxiety models [2].

High impact information on Lesopitron

• Forty-two patients with generalized anxiety disorder (GAD) were enrolled in this double-blind bridging study to determine the safety and tolerability of fixed doses of lesopitron (20, 25, 30, 40, 45, 50, and 60 mg two times a day) over a 6 1/2-day inpatient administration period [3].
• 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 [1].
• In Experiment 1, 14 healthy male volunteers participated in seven weekly sessions, 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 [1].
• In vitro binding and autoradiographic studies with [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) and [3H]lesopitron as radioligands confirmed that lesopitron binds to 5-HT1A receptors in the rat brain with a relatively high affinity (pKi = 7.35) [4].
• Lesopitron inhibits haloperidol-induced catalepsy that is the consequence of its action on 5-HT1A autoreceptors [5].

Chemical compound and disease context of Lesopitron

• OBJECTIVE: To compare the relative efficacy and safety of lesopitron 4-80 mg/d versus lorazepam 2-4 mg/d and placebo in a subgroup of patients with anxiety history taken from a larger study of patients with a primary diagnosis of generalized anxiety disorder (GAD) [6].

Biological context of Lesopitron

• The absolute bioavailability of lesopitron was about 10%, suggesting an important first-pass effect [7].

Anatomical context of Lesopitron

• Effects of lesopitron on the central nervous system arising from its interaction with 5-HT1A receptors [5].
• The drug behaved as antagonist at both 5-HT1A autoreceptors and postsynaptic 5-HT1A receptors, as it prevented the inhibitory effect of lesopitron on the electrical discharge of the dorsal raphé nucleus (DRN) 5-HT neurons and the activity of forskolin-stimulated adenylate cyclase in hippocampal homogenates [8].

Associations of Lesopitron with other chemical compounds

• Competitive prevention of the inhibition by the 5-HT1A receptor agonists 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin], 5-HT (5-hydroxytryptamine), S-20499 [(+)-4-(N-(5-methoxychroman-3-yl)-N-propylamino)butyl-8-azaspir o(4,5)decane- 7,9-dione] and lesopitron occurred with a pA2 of 8.7 for (+)-WAY 100 135 and 9.9 for SDZ 216-525 [9].
• WAY 100635 selectively blocked 5-HT1A receptor-mediated responses of 5-HT, 8-OH-DPAT, lesopitron and 5-CT [10].

Analytical, diagnostic and therapeutic context of Lesopitron

• Twenty healthy male volunteers participated in two weekly sessions, each associated with the sublingual application of 100 microl hydroalcoholic solution (lesopitron 20 mg, placebo), according to a double-blind balanced cross-over design [1].
• We investigated the effects of two 5-HT1A receptor agonists, buspirone and lesopitron, upon pupil size in human volunteers at an ambient luminance level of 32 Cd m(-2) and in darkness [1].
• The assay involves a solid-phase immobilization of IgG purified from polyclonal antiserum developed against the butylamino derivative of lesopitron covalently linked to bovine serum albumin [11].

References