ANTIPLATELET EFFECTS OF R,S-(MESO)-ALPHA, '-BIS[3-(N,N-DIETHYLCARBAMOYL)PIPERIDINO]-P-XYLENE EX-VIVO IN THE DOG AND IN-VIVO IN THE MOUSE

1. The nipecotamide '-bis[3-(N,N-diethylcarbamoyl)piperidino]-p-xylene (A-1) is a platelet aggregation inhibitor. The meso diastereomer A-1c is superior in potency and duration to the synthetic diastereomeric m ixture consisting of the R,R-, S,S-, and R,S- (meso) isomers in inhibi ting collagen-induced platelet aggregation ex vivo in the dog. 2. A-1c also is more potent and longer acting than A-1 in protecting mice fro m collagen+epinephrine-induced thromboembolic death. 3. The mechanism of antiplatelet action of this compound appears to be related to its a bility to prevent agonist-induced inhibition of platelet cyclic adenos ine monophosphate (cAMP) levels. (C) 1997 Elsevier Science Inc.