Induction of the platelet release reaction by 1.3-dimethyl-5-aminoadamantane, a new adamantane derivative.
The amantadine derivative 1.3-dimethyl-5-aminoadamantane, D 145, induces in high concentrations of 2-10 mM the release reaction. Adenine nucleotides and 5-hydroxytryptamine (5-HT) are liberated to the same extent and in the same ratio as found after thrombin-induced release. The time course of release is very slow; maximal release is reached in 15-20 min. The process is temperature-dependent and dependent on energy derived from glycolysis and oxidative phosphorylation. Extracellular Ca++ does not promote the release process. D 145, in accordance with the mother-substance amantadine, inhibits 5-HT uptake non-competitively, KI = 0.15mM. In concentrations of 0.1-1 mM D 145 triggers only the liberation of 5-HT, adenine nucleotides are not liberated. The ADP induced platelet aggregation is completely inhibited after preincubation with a 1 mM solution of D 145.
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000227:Adenine Nucleotides / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D001952:Bridged-Ring Compounds / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002118:Calcium; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D013696:Temperature; D013997:Time Factors
D000227:Adenine Nucleotides; D001952:Bridged-Ring Compounds; D012701:Serotonin; D000218:Adamantane; D002118:Calcium