Estudio de preformulación del citrato de dietilcarbamazina / Study of diethycarbamazine citrate preformulation

Se realizó el estudio de preformulación del citrato de dietilcarbamazina con el objetivo de conocer las características físico-químicas y tecnológicas de este fármaco para el posterior desarrollo de una tableta de 50 mg de dosis, el cual incluyó la determinación del tamaño de partícula micronizada y sin micronizar según el método de microscopia óptica, de manera que quedó demostrado la influencia que presenta éste en la disolución del fármaco in vitro. Se efectuó el estudio de incompatibilidad principio activo-excipientes mediante el método de calorimetría diferencial de barrido; no se encontró ninguna interacción entre éstos, en las condiciones de trabajo experimentales. Se estudiaron otras propiedades físico-químicas y tecnológicas del fármaco

5/6/7/8 mono or disubstituted 1H/1-phenyl-9H-pyrido [3,4 b] indoles--a new class of antifilarial agents and their relationship with voltage sensitive calcium channels in Setaria cervi.

Synthetic compounds of 5/6/7/8 mono or disubstituted 1H/1-phenyl-9H pyrido (3,4 b) indole series were screened for their antifilarial activity in vitro by observing their effect on the spontaneous movements of the whole worm and nerve muscle preparation of S. cervi (Nematoda:Filarioidea). Of the 10 compounds tested only compound 87/581 was able to modify the movements of whole worm and nerve muscle preparation. This compound caused inhibition of spontaneous motility of whole worm and nerve muscle preparation of S. cervi characterized by initial short lasting stimulation followed by irreversible paralysis. The concentration required to inhibit the movements of n.m. preparation was 10 micrograms/ml as compared to 25 micrograms/ml for the whole worm preparation, suggesting a cuticular permeability barrier. Prior addition of compound 87/581 to the bath fluid blocked the calcium ion dependent stimulant effect of Ach and pyrantel pamoate. Further the initial stimulant effect of the compound was blocked by prior addition of nifedipine a calcium channel blocker. The findings suggest that the action is due to blockade of voltage sensitive calcium channels.

Evaluation of vanillic acid analogues as a new class of antifilarial agents.

A number of vanillic acid analogues (1-14) have been synthesised and evaluated against experimental filarial infections using cotton rats (Sigmodon hispidus) infected with Litomosoides carinii, a primary screening model, at a dose of 30 mg/kg, ip for 5 days. Of the 8 compounds tested, 4 (5,7, 11 and 12) exhibited high micro- and macro-filaricidal activity with sterilization of surviving female worms. Compounds 5, 7, 12 showed remarkable adulticidal action (> 80%). Sterilization of the female worms by compounds 11 and 12 was highly significant (80-100%).