Antiplatelet effects of R,S-(meso)-alpha, alpha'-bis[3-(N,N-diethylcarbamoyl) piperidino]-p-xylene ex vivo in the dog and in vivo in the mouse.
1. The nipecotamide alpha,alpha'-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 mixture consisting of the R,R-, S,S-, and R,S- (meso) isomers in inhibiting 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 from collagen+epinephrine-induced thromboembolic death. 3. The mechanism of antiplatelet action of this compound appears to be related to its ability to prevent agonist-induced inhibition of platelet cyclic adenosine monophosphate (cAMP) levels.
Han
G
G
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee, Memphis 38163, USA.
Bannerman
D
D
Handa
R K
RK
Dillingham
E O
EO
Lawrence
W H
WH
Gollamudi
R
R
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D051379:Mice; D009557:Nipecotic Acids / Q000097:blood / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000494:pharmacology*; D013237:Stereoisomerism; D013923:Thromboembolism / Q000517:prevention & control*
D009557:Nipecotic Acids; D010975:Platelet Aggregation Inhibitors; C043099:alpha, alpha'-bis(3-(N,N-diethylcarbamoyl)piperidino)-4-xylene; D000242:Cyclic AMP