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Concentrations of 0.05, 0.01 and 0.2% propylthiouracil (PTU), incorporated into standard rat chow, induced hypothyroidism in male Sprague-Dawley rats following 6-8 weeks administration. The concentrations caused a progressive decrease in arterial blood pressure (BP), heart rate (HR), body weight (BW), food intake (FI), levels of triiodothyronine (T3), thyroxine (T4) and an increase in thyrotropin (TSH) levels. There was no clear-cut dose-dependent change in these parameters, since the values obtained for the 3 groups were not significantly different from one another, but were significantly lower than that of control rats (euthyroid). Pair-feeding studies between partial food-deprived euthyroid rats and PTU-induced hypothyroid rats showed that both types of treatment caused a decrease in BW, BP, HR, colonic temperature, levels of T3, T4 and an increase in TSH. The changes were significantly (P less than .05) greater in the hypothyroid than in the food deprived rats at the end of the 6th week and thereafter.

N, N-Diethylaminoethyl ester and 3-quinuclidinyl ester of 2, 2-diphenylpropanoic acid (compound 1 and 2, respectively) were prepared and pharmacologically evaluated in vitro and in the intact animal. Both compounds attenuated the effects of increasing doses of ACh in the isolated rat ileum (pA2 = 8.40 and 8.55, respectively). These effects were comparable to that of atropine (pA2 = 8.73). The duration of methacholine-induced salivation in male Swiss-Webster mice was significantly decreased by compound 2 but not by compound 1. Cardiorespiratory studies in adult male Sprague-Dawley rats revealed that both compounds shifted the dose-response curves to methacholine in terms of arterial blood pressure, heart rate and respiration upwards; indicative of cholinergic blockade. The observed pharmacological differences between the two compounds may be attributed to apparent in vivo hydrolysis of compound 1 by esterases.

Dietary administration of propylthiouracil (0.2%) to male Sprague-Dawley rats for a period of 8 weeks induced hypothyroidism and hypotension in these animals. Resting heart rate, body weight, colonic temperature and serum thyroxine (T4) were significantly lower in the treated hypothyroid rats than in the controls. Time-course study indicates that the maximal depression of these parameters occurred about the eighth week of PTU treatment; except T4 level which declined abruptly about the second week and remained steady thereafter. The mechanism(s) of hypotension is (are) unknown but there seems to be an interrelationship between hypothyroidism-induced hypotension and the parameters monitored, since discontinuation of PTU treatment reversed that trend of the response toward control levels.