Inhibitory effects of H2-receptor antagonists on platelet function in vitro.
To evaluate in vitro inhibitory effects of four types of histamine H2-receptor antagonist (H2-receptor antagonists), famotidine, roxatidine, cimetidine and ranitidine, on platelet function, we examined aggregating potency and P-selectin levels with agonist-induced aggregation. Ranitidine and cimetidine inhibited, in concentration of 0.35 mM, the secondary aggregation induced by 5 microM adenosine diphosphate (ADP), the aggregation induced by 1 microg/mL collagen and 3 microM arachidonic acid. All of H2-receptor antagonists inhibited, in concentration of 1.4 mM, the aggregation induced by ADP, collagen and arachidonic acid. Ranitidine and cimetidine reduced markedly, in same concentration, P-selectin levels after induction of aggregation by 5 microm ADP, 1 microg/mL collagen and 3 microM arachidonic acid. When classified by the strength of inhibitory action, ranitidine and cimetidine were strong, followed by famotidine and roxatidine. It is considered that inhibitory effects of H2-receptor antagonists on platelet function are weaker than those of acetylsalicylic acid (ASA), since ASA inhibited platelet aggregation in concentration of 100 microM. No relationship was observed between inhibitory effects of H2-receptor antagonists on platelet aggregation induced by above agonists and the presence or absence of imidazole ring in the chemical structure.
Nakamura
K
K
Department of Hospital Pharmacy, Faculty of Medicine, Kagoshima University, Japan.
Kariyazono
H
H
Shinkawa
T
T
Yamaguchi
T
T
Yamashita
T
T
Ayukawa
O
O
Moriyama
Y
Y
Yotsumoto
G
G
Toyohira
H
H
Taira
A
A
Yamada
K
K
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002927:Cimetidine / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D015738:Famotidine / Q000494:pharmacology; D005260:Female; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011899:Ranitidine / Q000494:pharmacology; D013329:Structure-Activity Relationship
D006573:Heterocyclic Compounds, 1-Ring; D006635:Histamine H2 Antagonists; D019007:P-Selectin; D010880:Piperidines; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D015738:Famotidine; D000244:Adenosine Diphosphate; D002927:Cimetidine; D011899:Ranitidine; D003094:Collagen; D001241:Aspirin; C053742:roxatidine acetate