Relationships between the chemical constitution of aggregation inhibitors and human blood platelet response profile.
Gradually altered synthetic entities were employed as molecular probes, and arachidonic acid, ADP, human alpha-thrombin and the Ca2+ ionophore A23187 as aggregation-inducing agents, in a comprehensive study on the response profile of human blood platelets with an emphasis on the effects of exogenous and increased intracellular Ca2+. Corroborating further previous conclusions, some representative carbamoylpiperidine derivatives, at concentrations effecting substantial inhibition of ADP-induced aggregation, failed to retain that effect when 5.0 mM Ca2+ was introduced into the otherwise identical test medium; reference compounds chlorpromazine and propranolol registered corresponding inhibitory patterns. At increased concentrations the compounds' inhibitory potency was regenerated even in the presence of 5 mM Ca2+. In fact, in sufficiently high concentrations, the compounds were even capable of inhibiting aggregation elicited by 15 microM of the ionophore A23187; so did chlorpromazine and propranolol. Another set of congeners revealed the striking sensitivity of ionophore A23187-induced human blood platelet aggregation to the surface active potencies of inhibitor molecules. The loss in inhibitory potency was directly related to the lesser hydrophobic character of the molecule.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010880:Piperidines / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D002219:Carbamates; D010880:Piperidines; D016718:Arachidonic Acid; D000001:Calcimycin; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D000244:Adenosine Diphosphate; D005707:Gallic Acid; D011433:Propranolol; D013917:Thrombin; D001241:Aspirin; D002118:Calcium; D002746:Chlorpromazine