Biomaterial Database

LY53857, a 5HT2 receptor antagonist, delays occlusion and inhibits platelet aggregation in a rabbit model of carotid artery occlusion. 1991

H C Wilson, and W Coffman, and A L Killam, and M L Cohen

Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285.

The present study was designed to evaluate the effectiveness of the ergoline 5HT2 receptor antagonist, LY53857 in a rabbit model of vascular arterial occlusion. LY53857 (1 and 10 microM) inhibited serotonin amplified platelet aggregation responses to threshold concentrations of ADP in rabbit platelets in vitro. LY53857 (1 microM) not only inhibited the serotonin component of rabbit platelet aggregation, but also inhibited in vitro aggregation induced by ADP (48.7 +/- 16.7% inhibition), collagen (76.1 +/- 15.9% inhibition) and U46619 (65.2 +/- 12.3% inhibition). The effectiveness of this ergoline 5HT2 receptor antagonist in blocking aggregation to ADP, collagen and U46619 may be related to its ability to inhibit a serotonin component of platelet aggregation since rabbit platelets possess high concentrations of serotonin that may be released during aggregation produced by other agents. Based on the effectiveness of LY53857 to inhibit rabbit platelet aggregation, we explored the ability of LY53857 to extend the time to carotid artery occlusion in rabbits following electrical stimulation of the artery. Reproducible carotid artery occlusion was induced in rabbits by moderate stenosis coupled to arterial cross clamping, followed by electrical stimulation. With this procedure, occlusion occurred at 47.0 +/- 7 min (n = 30) after initiation of the electrical stimulation. Animals pretreated with LY53857 (50 to 500 micrograms/kg i.v.) showed a delay in the time to carotid artery occlusion (at 100 micrograms/kg i.v. occlusion time extended to 164 +/- 16 min). Furthermore, ex vivo platelet aggregation from animals treated with LY53857 (300 micrograms/kg i.v.) resulted in 40.5% inhibition of platelet aggregation in response to the combination of ADP (1 microM) and serotonin (1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010975	Platelet Aggregation Inhibitors	Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.	Antiaggregants, Platelet,Antiplatelet Agent,Antiplatelet Agents,Antiplatelet Drug,Blood Platelet Aggregation Inhibitor,Blood Platelet Antagonist,Blood Platelet Antiaggregant,PAR-1 Antagonists,Platelet Aggregation Inhibitor,Platelet Antagonist,Platelet Antagonists,Platelet Antiaggregant,Platelet Antiaggregants,Platelet Inhibitor,Protease-Activated Receptor-1 Antagonists,Antiplatelet Drugs,Blood Platelet Aggregation Inhibitors,Blood Platelet Antagonists,Blood Platelet Antiaggregants,Platelet Inhibitors,Agent, Antiplatelet,Aggregation Inhibitor, Platelet,Antagonist, Blood Platelet,Antagonist, Platelet,Antiaggregant, Blood Platelet,Antiaggregant, Platelet,Drug, Antiplatelet,Inhibitor, Platelet,Inhibitor, Platelet Aggregation,PAR 1 Antagonists,Platelet Antagonist, Blood,Platelet Antiaggregant, Blood,Protease Activated Receptor 1 Antagonists
D011817	Rabbits	A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes.	Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D002340	Carotid Artery Diseases	Pathological conditions involving the CAROTID ARTERIES, including the common, internal, and external carotid arteries. ATHEROSCLEROSIS and TRAUMA are relatively frequent causes of carotid artery pathology.	Carotid Atherosclerosis,Common Carotid Artery Disease,Internal Carotid Artery Disease,Arterial Diseases, Carotid,Arterial Diseases, Common Carotid,Arterial Diseases, External Carotid,Arterial Diseases, Internal Carotid,Atherosclerotic Disease, Carotid,Carotid Artery Disorders,Carotid Atherosclerotic Disease,Common Carotid Artery Diseases,External Carotid Artery Diseases,Internal Carotid Artery Diseases,Arterial Disease, Carotid,Artery Disease, Carotid,Artery Diseases, Carotid,Artery Disorder, Carotid,Artery Disorders, Carotid,Atherosclerotic Diseases, Carotid,Carotid Arterial Disease,Carotid Arterial Diseases,Carotid Artery Disease,Carotid Artery Disorder,Carotid Atheroscleroses,Carotid Atherosclerotic Diseases,Disorders, Carotid Artery
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004873	Ergolines	A series of structurally-related alkaloids that contain the ergoline backbone structure.	Ergoline
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001157	Arterial Occlusive Diseases	Pathological processes which result in the partial or complete obstruction of ARTERIES. They are characterized by greatly reduced or absence of blood flow through these vessels. They are also known as arterial insufficiency.	Arterial Obstructive Diseases,Arterial Occlusion,Arterial Obstructive Disease,Arterial Occlusions,Arterial Occlusive Disease,Disease, Arterial Obstructive,Disease, Arterial Occlusive,Obstructive Disease, Arterial,Occlusion, Arterial,Occlusive Disease, Arterial
D012702	Serotonin Antagonists	Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.	5-HT Antagonist,5-HT Antagonists,5-Hydroxytryptamine Antagonist,5-Hydroxytryptamine Antagonists,Antiserotonergic Agent,Antiserotonergic Agents,Serotonin Antagonist,Serotonin Blockader,Serotonin Blockaders,Serotonin Receptor Antagonist,Serotonin Receptor Blocker,Antagonists, 5-HT,Antagonists, 5-Hydroxytryptamine,Antagonists, Serotonin,Serotonin Receptor Antagonists,Serotonin Receptor Blockers,5 HT Antagonist,5 HT Antagonists,5 Hydroxytryptamine Antagonist,5 Hydroxytryptamine Antagonists,Agent, Antiserotonergic,Agents, Antiserotonergic,Antagonist, 5-HT,Antagonist, 5-Hydroxytryptamine,Antagonist, Serotonin,Antagonist, Serotonin Receptor,Antagonists, 5 HT,Antagonists, 5 Hydroxytryptamine,Antagonists, Serotonin Receptor,Blockader, Serotonin,Blockaders, Serotonin,Blocker, Serotonin Receptor,Blockers, Serotonin Receptor,Receptor Antagonist, Serotonin,Receptor Antagonists, Serotonin,Receptor Blocker, Serotonin,Receptor Blockers, Serotonin
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor