RESUMO
RATIONALE: Flesinoxan is a highly potent and selective 5-HT1A agonist. In a recent study, in normal volunteers, flesinoxan induced a significant and dose-dependent increase in adrenocorticotropic hormone (ACTH), cortisol, prolactin (PRL), growth hormone (GH) and a decrease in body temperature. OBJECTIVES: In order to better define the role of 5-HT receptor subtypes in response to flesinoxan, we assessed the influence of 5-HT1A and 5-HT2 antagonists on hormonal and temperature responses to flesinoxan. METHODS: Hormonal and temperature responses were studied in 6 volunteers with or without pretreatment with pindolol (30 mg p.o.), a 5-HT1A antagonist, or ritanserin (10 mg p.o.), a selective 5-HT2 antagonist, using a double-blind crossover design. RESULTS: Pindolol significantly antagonized ACTH, PRL, GH and temperature responses to flesinoxan and ritanserin exhibited similar activity on PRL and ACTH responses. CONCLUSIONS: These results show the role of 5-HT1A mechanisms in the PRL, ACTH, GH, and temperature responses to flesinoxan, and the role of 5-HT2 mechanisms in PRL and ACTH responses. Therefore, they confirm the interest of flesinoxan as a 5-HT neuroendocrine probe.
Assuntos
Temperatura Corporal/efeitos dos fármacos , Hormônios/sangue , Piperazinas/farmacologia , Receptores de Serotonina/fisiologia , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Hormônio Adrenocorticotrópico/sangue , Adulto , Pressão Sanguínea/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Avaliação de Medicamentos , Interações Medicamentosas , Hormônio do Crescimento/sangue , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hidrocortisona/sangue , Masculino , Pindolol/farmacologia , Prolactina/sangue , Radioimunoensaio/métodos , Ritanserina/farmacologia , Fatores de TempoRESUMO
RATIONALE: Flesinoxan is a highly potent and selective 5-HT(1A) agonist and appears to be a potentially interesting neuroendocrine serotonergic probe. OBJECTIVES: We assessed hormonal (ACTH, cortisol, prolactin and growth hormone) and temperature responses to flesinoxan in normal volunteers. METHODS: In a double-blind placebo-controlled study, single doses of 0.5 mg and 1 mg were injected over 10 min into 12 healthy male volunteers at 1-week intervals. Temperature and hormonal responses were measured at times -30, 0, 15, 30, 60, 90, and 120 min. RESULTS: Flesinoxan induced a significant and dose-dependent increase in adrenocorticotropic hormone (ACTH), cortisol, prolactin (PRL), growth hormone (GH) and a decrease in body temperature. Tolerance to flesinoxan was excellent. CONCLUSIONS: These results showed the role of 5-HT(1A) mechanisms in the PRL, ACTH, cortisol, GH, and temperature responses to flesinoxan. In the present study, flesinoxan appears a very promising serotonergic neuroendocrine probe.
