Amitriptyline-induced constipation in cynomolgus monkeys is beneficial forthe evaluation of laxative efficacy

In an attempt to create an animal model of constipation in monkeys, amitrip tyline was administered to cynomolgus monkeys at doses of 10-160 mg/kg body weight,lia a nasogastric tube. Normal control monkeys excreted feces frequ ently throughout the day, Monkeys treated with amitriptyline at doses of 10 -40 mg/kg showed delays in feces excretion. The 60 mg/kg treated monkeys fo r the most part did not excrete feces during the 24 h after amitriptyline a dministration. The 80 and 120 mg/kg treated monkeys did not excrete feces u ntil 24 h from administration of amitriptyline, and also showed prolonged c rouching and lethargy On the other hand, 160 mg/kg treated monkeys died wit hin 24 h after administration. We therefore felt that the optimal dose for creating constipation in the monkeys was 60 mg/kg, We tested the appropriat eness of this amitriptyline-induced constipated monkey model by observing t he effects of a new laxative, the herbal medicine ND-10 and the commerciall y available laxative bisacodyl, Control monkeys (those not receiving ND-10 or bisacodyl) treated with 60 mg/kg amitriptyline did not excrete feces up to 32 h after amitriptyline administration in 2 of 3 monkeys. However, all monkeys treated with one tablet of ND-10 excreted feces. Also, in 4 monkeys administrated with bisacodyl, 3 excreted feces, In this study, me confirme d that constipation can be caused in cynomolgus monkeys by oral administrat ion of amitriptyline. This model may also be useful for the evaluation of l axatives.