Sedative-hypnotic profile of novel isatin ketals.
Isatin (1H-indol-2,3-dione) is an endogenous compound found in many tissues and fluids. Isatin and its derivatives exert pharmacological effects on the central nervous system, including anxiogenic, sedative and anticonvulsant activities. Two new groups of isatin derivatives were synthesized (nine dioxolane ketals and nine dioxane ketals) and studied for their sedative, hypnotic and anesthetic effects using pentobarbital-induced sleeping time, locomotor activity evaluation and intravenous infusion. The dioxolane ketals were more potent than dioxane ketals for inducing sedative-hypnotic states, causing up to a three-fold increase in pentobarbital hypnosis. The dioxolane ketals produced sedation, demonstrated by decreased spontaneous locomotor activity in an open field. Hypnosis and anesthesia were observed during intravenous infusion of 5'-chlorospiro-[1,3-dioxolane-2,3'-indolin]-2'-one (T3) in conscious Wistar rats. Complete recovery from hypnosis and anesthesia required 39.1+/-7.3 and 6.8+/-2.4 min, respectively. Changes in hemodynamic parameters after infusion of 5.0 mg/kg/min were minimal. These findings suggest that these new isatin derivatives represent potential candidates for the development of new drugs that act on the central nervous system and may lead to a new centrally acting anesthetic with no toxic effects on the cardiovascular or respiratory systems.
Zapata-Sudo
Gisele
G
Departamento de Farmacologia Básica e Clínica, Universidade Federal do Rio de Janeiro, Centro de Ciên cias da Saúde, Instituto de Ciências Biomédicas, Bloco J, Sala 14, Rio de Janeiro, 21941-590, Brazil. gsudo@farmaco.ufrj.br
Pontes
Luana B
LB
Gabriel
Daniele
D
Mendes
Thaiana C F
TC
Ribeiro
Núbia M
NM
Pinto
Angelo C
AC
Trachez
Margarete M
MM
Sudo
Roberto T
RT
D000818:Animals; D004353:Drug Evaluation, Preclinical; D006993:Hypnotics and Sedatives / Q000737:chemistry / Q000494:pharmacology*; D007510:Isatin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects; D013329:Structure-Activity Relationship
D006993:Hypnotics and Sedatives; D007510:Isatin; D010424:Pentobarbital