Relationships between chemical structure and inhibition of ADP-stimulated human thrombocyte release of serotonin and platelet factor 4.
The inhibitory potencies of carbamoylpiperidinoalkane and N-alkylnipecotoylpiperazine derivatives on ADP-stimulated human blood platelet aggregation, serotonin (5-HT) release and platelet factor 4 (PF-4) release were evaluated. The procedure was designed to allow concurrent determination of all three sets of values. Most compounds were more than twice as potent in blocking PF-4 (X = 91 +/- 1 (S.E., n = 7)%) compared to their inhibition of 5-HT (X = 38 +/- 1(S.E., n = 6)%) release; the one compound which failed to meet these criteria was still decidedly more powerful in impeding PF-4 than 5-HT release. Since the compounds' platelet aggregation-inhibitory values were within the same range as their 5-HT release-blocking potencies, but had a strikingly greater impact in arresting PF-4 release, it is suggested that the platelet plasma membrane and the lining enveloping the dense bodies may share certain commonalities, while the sheathing encasing the alpha-granules may differ from both in a tangible manner.
Dillingham
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EO
Department of Medicinal Chemistry, College of Pharmacy, University of Tennessee, Memphis 38163.
Lasslo
A
A
Carter-Burks
G
G
Bond
S E
SE
Gollamudi
R
R
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015335:Molecular Probes; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010978:Platelet Factor 4 / Q000097:blood*; D012701:Serotonin / Q000097:blood*; D013329:Structure-Activity Relationship
D015335:Molecular Probes; D010879:Piperazines; D010880:Piperidines; D012701:Serotonin; D010978:Platelet Factor 4; D000244:Adenosine Diphosphate