Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Inhibitors of platelet signal transduction as anti-aggregatory drugs
Autore:
Geiger, J;
Indirizzi:
Univ Wurzburg, Med Clin, Inst Clin Biochem & Pathobiochem, Wurzburg, Germany Univ Wurzburg Wurzburg Germany iochem & Pathobiochem, Wurzburg, Germany
Titolo Testata:
EXPERT OPINION ON INVESTIGATIONAL DRUGS
fascicolo: 5, volume: 10, anno: 2001,
pagine: 865 - 890
SICI:
1354-3784(200105)10:5<865:IOPSTA>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
THROMBOXANE SYNTHASE INHIBITOR; DEPENDENT PROTEIN-KINASE; VASCULAR SMOOTH-MUSCLE; CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BIOLOGICALLY-ACTIVE COMPOUNDS; ACUTE MYOCARDIAL-INFARCTION; PROSTAGLANDIN G/H SYNTHASE; OXIDE RELEASE ACCOUNTS; HUMAN-BLOOD-PLATELETS;
Keywords:
antiplatelet drugs; cyclooxygenase inhibitor; endothelial factors; phosphodiesterase inhibitor; thromboxane synthase inhibitor;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
205
Recensione:
Indirizzi per estratti:
Indirizzo: Geiger, J Univ Wurzburg, Med Clin, Inst Clin Biochem & Pathobiochem, Wurzburg, Germany Univ Wurzburg Wurzburg Germany athobiochem, Wurzburg, Germany
Citazione:
J. Geiger, "Inhibitors of platelet signal transduction as anti-aggregatory drugs", EXPERT OP I, 10(5), 2001, pp. 865-890

Abstract

In the treatment and prevention of cardiovascular diseases, inhibition of platelet aggregation is of fundamental importance. Inhibition of platelet aggregation can be achieved by either inhibition of membrane receptors or byinterception of signalling pathways. While receptor antagonism provides high specificity. the inhibition of platelet signal transduction is more effective. The effectiveness results from the inhibition of platelets. regardless of the cause of activation These common pathway inhibitors are either intercepting platelet activating mechanisms or amplifying the action of endogenous platelet inhibitors. The physiological anti-aggregants are the endothelial factors NO and prostacyclin, which elevate intracellular cGMP or cAMPcontent, respectively. By administration of NO-releasing agents. prostacyclin analogues or other cyclic nucleotide elevating drugs the: platelet anti-aggregatory action of endothelial factors can be effectively mimicked. Besides antiplatelet activity these drugs also act on vascular smooth muscle causing relaxation and therefore vasodilation, an additional beneficial effect. Inhibition of phosphodiesterases causes elevation of platelet cyclic nucleotide content and thus inhibits platelet aggregation and causes vasodilation. Another relevant target for anti-aggregatory treatment is the arachidonic acid metabolic pathway. This pathway can be intercepted by blockade ofeither cyclooxygenase-1 (COX-1) or thromboxane synthase. Inhibition of these enzymes may be further amplified by additional antagonism of the thromboxane receptor thus not only preventing formation of thromboxane but also activation of thromboxane receptor by thromboxane precursors. which were particularly effective in clinical trials. In vitro these precursors may be metabolised ro prostacyclin in the endothelium and consequently provide additional platelet anti-aggregatory activity. A rather nem; target fur platelet anti-aggregatory treatment is the ecto-nucleotidase CD-39 which limits the plasma level of nucleotides. While several of the novel anti-aggregatory drugs were disappointing in clinical studies combinations of drugs with different effector enzymes showed potent antithrombotic efficacy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/20 alle ore 18:19:35