Effect of KBT-3022, a new diphenylthiazole derivative, on platelet functions.
The effects of KBT-3022 and its metabolite desethyl KBT-3022 on platelet aggregation were determined in rat, guinea-pig, rabbit and human platelets in-vitro and ex-vivo. KBT-3022 and desethyl KBT-3022 inhibited platelet aggregation induced by arachidonic acid and collagen in-vitro more potently than aggregation induced by adenosine diphosphate, platelet-activating factor or thrombin, as well as by acetylsalicylic acid, and their effects were approximately 100 times more potent than those of acetylsalicylic acid. Desethyl KBT-3022, but not KBT-3022 or acetylsalicylic acid, inhibited thrombin-induced aggregation and 5-hydroxytryptamine release from platelets more potently than ticlopidine hydrochloride at higher concentrations. Oral administration of KBT-3022 inhibited both arachidonic acid- and collagen-induced platelet aggregation and reduced platelet retention in a glass-bead column approx. 100 times more potently than acetylsalicylic acid. KBT-3022 showed little or no anti-inflammatory effect on either ultraviolet-induced erythema or arachidonic acid induced ear oedema, and had lower gastro-ulcerogenicity than acetylsalicylic acid. These results suggest that KBT-3022 is a potent inhibitor of platelet activation with weak side-effects.
Yokota
K
K
New Drug Research Laboratories, Kanebo, Ltd., Osaka, Japan.
Yamamoto
N
N
Morimoto
Y
Y
Yamashita
A
A
Oda
M
M
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D003094:Collagen / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced; D004890:Erythema / Q000139:chemically induced; D005753:Gastric Mucosa / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D013045:Species Specificity; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology; D014466:Ultraviolet Rays / Q000009:adverse effects
D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; D013844:Thiazoles; C064847:KB 3022; D016718:Arachidonic Acid; D012701:Serotonin; D000244:Adenosine Diphosphate; D003094:Collagen; D013917:Thrombin; D001241:Aspirin