Avaliação dos efeitos farmacológicos de (O-Metil)-N-2-Hidroxi-Benzoil Tiramina (Riparina Ii) de Aniba riparia (Nees) Mez (Lauraceae) em modelos comportamentais de ansiedade e depressão em camundongos

Abstract

Riparin II, an alkamide isolated from unripe fruit of Aniba riparia, was evaluated in animal classical models for screening of new drugs in anxiety, depression, sedation and convulsion, such as, open field, rota rod, plus maze, hole board, forced swimming, tail suspension, pentobarbital-induced sleeping time and pentilenotetrazole-induced seizures tests. Riparin II was administered acutely in all tests, at doses of 25 e 50 mg/kg, and at dose 75 mg/kg in open field, rota rod, plus maze and tail suspension tests, through oral and intraperitoneal routes. The results showed that this alkamide did not alter the locomotor activity and grooming, but decreased the number of rearing in the open field test, suggesting a possible anxiolytic effect. In the plus maze and hole board tests, riparin II presented anxiolytic effect due to an increase in all parameters analyzed, such as, NEOA, PEOA, TPOA and PTOA, in the plus maze, and an increase in the number of head dips in the hole board test. This effect is possible related with GABAergic system, since flumazenil, an antagonist of GABAA/Benzodiazepinic receptors, reversed the anxiolytic effect of riparin II, in the plus maze test. The sedative/hypnotic evaluation of riparin II, in pentobarbital-induced sleeping time, showed a sleeping potentiation that seems to be involved with pharmacokinetic processes or sleeping regulation mechanisms, since the sedative effect of riparin II was not corroborated in the open field test. In the pentilenotetrazole-induced seizures test, riparin II partially protected the animals from seizures, increased the death time, and in some cases, even protected the animals from death. This result may suggest an anticonvulsant effect of riparin II, possible related to GABAergic system, since there is an involvement of this substance with GABAA/Benzodiazepinic receptor, seen in plus maze test. Riparin II also presents an antidepressant effect, since in the forced swimming and tail suspension tests, this substance decreased the immobility time of the animals. The antidepressant effect of riparin II seems to be related with dopaminergic and noradrenergic systems. The antagonists of D1 and D2 dopaminergic receptor, SCH23390 and sulpiride, reverted riparin II effect in the forced swimming test. The antagonist of α1 adrenergic receptor, prazosin, reverted riparin II effect in the forced swimming test. However, the antagonist of α2 adrenergic receptor, yohimbine, did not revert this effect. This result suggests that the antidepressant effect of this alkamide is involved with dopaminergic system, with D1 and D2 dopaminergic receptor, and noradrenergic systems, specifically with α1 adrenergic receptor. In conclusion, these efects showed that riparin II presents anxiolytic and anticonvulsant effects, probably related with GABAergic system, and presents antidepressant effect, probably related with dopaminergic and noradrenergic systems.