caa a22 4500 465738826 CHVBK 20180323111802.0 cr unu---uuuuu 170327e19900301xx s 000 0 eng 10.1007/BF02245790 doi (NATIONALLICENCE)springer-10.1007/BF02245790 Acute reversal of flunitrazepam effects by Ro 15-1788 and Ro 15-3505: inverse agonism, tolerance, and rebound [Elektronische Daten] [V. Gentil, S. Tavares, C. Gorenstein, C. Bello, L. Mathias, G. Gronich, J. Singer] A phase 1 double blind crossover comparison of a new benzodiazepine antagonist (Ro 15-3505) with Ro 15-1788 and placebo, in the reversal of sedative and psychophysiological effects of single IV doses of flunitrazepam (2 mg), was carried out in 12 normal volunteers. The antagonists were equally effective, leading to full reversal of all effects with a potency ratio of approximately 2.5 mg Ro 15-1788 for 1 mg Ro 15-3505. Inverse agonism, in the form of unpleasant feelings and symptoms, was reported by all subjects following Ro 15-3505 but none after Ro 15-1788. Adaptational phenomena such as acute tolerance and rebound of sedative effects of flunitrazepam were also detected and their potential implications are discussed. Springer-Verlag, 1990 Benzodiazepine antagonists nationallicence Inverse agonism nationallicence Tolerance nationallicence Rebound nationallicence Flunitrazepam nationallicence Gentil V. Departmento de Psiquiatria, Faculdade de Medicina, USP, Caixa Postal 8091, São Paulo, Brazil aut Tavares S. Instituto de Psiquiatria, Hospital das Clinicas, Brazil aut Gorenstein C. Departmento de Farmacologia, Instituto de Ciências Biomédicas, Brazil aut Bello C. Disciplina de Anestesiologia, Hospital das Clínicas, Brazil aut Mathias L. Disciplina de Anestesiologia, Hospital das Clínicas, Brazil aut Gronich G. Instituto de Psiquiatria, Hospital das Clinicas, Brazil aut Singer J. Departmento de Estatística, Instituto de Matemática e Estatística, Universidade de São Paulo, Brazil aut Psychopharmacology Springer-Verlag 100/1(1990-03-01), 54-59 0033-3158 100:1<54 1990 100 213 https://doi.org/10.1007/BF02245790 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02245790 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gentil V. Departmento de Psiquiatria, Faculdade de Medicina, USP, Caixa Postal 8091, São Paulo, Brazil aut NATIONALLICENCE 700 1- Tavares S. Instituto de Psiquiatria, Hospital das Clinicas, Brazil aut NATIONALLICENCE 700 1- Gorenstein C. Departmento de Farmacologia, Instituto de Ciências Biomédicas, Brazil aut NATIONALLICENCE 700 1- Bello C. Disciplina de Anestesiologia, Hospital das Clínicas, Brazil aut NATIONALLICENCE 700 1- Mathias L. Disciplina de Anestesiologia, Hospital das Clínicas, Brazil aut NATIONALLICENCE 700 1- Gronich G. Instituto de Psiquiatria, Hospital das Clinicas, Brazil aut NATIONALLICENCE 700 1- Singer J. Departmento de Estatística, Instituto de Matemática e Estatística, Universidade de São Paulo, Brazil aut NATIONALLICENCE 773 0- Psychopharmacology Springer-Verlag 100/1(1990-03-01), 54-59 0033-3158 100:1<54 1990 100 213 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer