Synthesis, antispasmodic and antidiarrheal activities of some 1-substituted imidazole derivatives

A series of 1-substituted imidazoles 1a-d and 2a-d were synthesized and screened for antispasmodic and antidiarrheal activities. Antispasmodic activity was tested at various concentrations on isolated tissue preparations; concentration-response curves were plotted and compared with atropine. All compounds were found to inhibit contraction of the guinea pig ileum. Castor oil-induced diarrhea model in rats was used for evaluation of antidiarrheal activity. Parameters such as intestinal transit and volume of intestinal fluid were measured for antidiarrheal activity at 40 mg kg-1 dose and compared with the standard drug loperamide at 6 mg kg-1 dose. Defecation frequency in the test group was found to be significantly lower (p < 0.01) compared to the control group and comparable with that of the standard. The present study reveals that the compounds exert antidiarrheal activity through possible inhibition of intestinal movement and reduction of capillary permeability in the abdominal cavity. U radu je opisana sinteza serije novih 1-supstituiranih imidazola 1a-d i 2a-d te evaluacija njihovog spazmolitskog i antidijaretskog djelovanja. Spazmolitsko djelovanje različ ith koncentracija ispitivanih spojeva (10, 50 i 100 μg mL-1) ispitano je na izoliranim tkivnim preparatima; krivulje ovisnosti djelovanja o koncentraciji uspoređene su s djelovanjem atropina. Svi ispitivani spojevi inhibirali su kontrakcije ileuma zamorca. Dijarea inducirana ricinusovim uljem u štakora korištena je za vrednovanje antidijaretskog djelovanja. Intestinalni prijenos i volumen intestinalne tekućine mjereni su pri dozi od 40 mg kg-1 i uspoređeni s učinkom standarda loperamida (doza 6 mg kg-1). Učestalost defekacije u testiranoj skupini bila je značajno niža (p < 0,01) u usporedbi s kontrolnom skupinom i standardom. Provedena ispitivanja pokazuju da antidijaretsko djelovanje ispitivanih spojeva može biti posljedica inhibicije intestinalnih pokreta i redukcije kapilarne permeabilnosti u abdominalnoj šupljini.