Zapata-Sudo Gisele, Pontes Luana B, Gabriel Daniele, Mendes Thaiana C F, Ribeiro Núbia M, Pinto Angelo C, Trachez Margarete M, Sudo Roberto T
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.
Pharmacol Biochem Behav. 2007 Apr;86(4):678-85. doi: 10.1016/j.pbb.2007.02.013. Epub 2007 Feb 22.
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.
异吲哚酮（1H-吲哚-2,3-二酮）是一种存在于许多组织和体液中的内源性化合物。异吲哚酮及其衍生物对中枢神经系统具有药理作用，包括产生焦虑、镇静和抗惊厥活性。合成了两组新的异吲哚酮衍生物（九种二氧戊环缩酮和九种二氧六环缩酮），并通过戊巴比妥诱导的睡眠时间、运动活性评估和静脉输注研究了它们的镇静、催眠和麻醉作用。二氧戊环缩酮在诱导镇静催眠状态方面比二氧六环缩酮更有效，可使戊巴比妥诱导的催眠作用增强至三倍。二氧戊环缩酮产生了镇静作用，这通过在旷场中自发运动活性降低得到证明。在清醒的Wistar大鼠静脉输注5'-氯螺[1,3-二氧戊环-2,3'-吲哚]-2'-酮（T3）期间观察到了催眠和麻醉作用。从催眠和麻醉状态完全恢复分别需要39.1±7.3分钟和6.8±2.4分钟。以5.0毫克/千克/分钟的速度输注后，血流动力学参数的变化最小。这些发现表明，这些新的异吲哚酮衍生物是开发作用于中枢神经系统的新药的潜在候选物，可能会导致一种对心血管或呼吸系统无毒性作用的新型中枢作用麻醉剂。
