Joseph P. Buyniski

Behavioral suppressant effects of clonidine in strains of normotensive and hypertensive rats

The behavioral effects of orally administered clonidine were investigated in Long--Evans (LE), Sprague--Dawley (SD) or Kyoto Wistar (KW) rats assumed to be normotensive and in NIH spontaneously hypertensive (SH) rats. Although clonidine (0.05-1 mg/kg) resulted in the same qualitative effect, i.e., depression of motor activity, the dose of clonidine required to depress motor activity to 50% of control levels (ED50) tended to vary according to strain. An analysis of variance of the dose response curves for the four strains of rats indicated a significant strain effect. When the effects of clonidine on food-reinforced operant responding were investigated it was observed that SD and SH rats differed with regard to rate and temporal pattering of IRT greater than 20 sec responding. Although oral administration of clonidine (0.006-0.1 mg/kg) produced similar percentage decreases from control in SH and SD rats, and analysis of the temporal patterning of responding indicated differences in responsiveness to the behavioral effects of clonidine. These studies demonstrate strain-related differences in responsiveness to the behavioral suppressant effects of clonidine. Marked differences between genetically hypertensive rats and rats assumed to be normotensive were not evident.

Potential non-dopaminergic gastrointestinal prokinetic agents in the series of substituted benzamides

Abstract A series of 2-substituted-4-amino-5-chloro-N-[2-diethylaminoethyl]benzamides was synthesized and evaluated for gastrointestinal motility enhancing activity in vitro (enhancement of field stimulated guinea pig ileum test) and in vivo (enhancement of rat stomach emptying). A number of compounds were shown to be potent gastrointestinal prokinetic agents yet were devoid of dopaminergic D2-receptor antagonism as shown by their inability to displace [3H]spiperone from brain membranes. The model compound 6b would be expected to have clinical use in a spectrum of upper gastroinstestinal motility disorders but without the central nervous system side effects characteristic of dopaminergic D2-receptor blockade in the brain.

Isosteric replacement in a series of β-substituted monophosphonate calcium antagonists

Abstract A series of β-substituted phosphonate derivatives was prepared by standard routes and the Ca ++ channel inhibitory properties of the compounds examined in rat brain and aorta. The results indicate the certain ester substituents can serve as effective phosphonate replacements. The most potent calcium antagonist identified from the series was the β-substituted hexanoyl ester derivative BMY-43011 ( 5f ).