PHARMACODYNAMIC PROFILE OF PROSTACYCLIN

被引:216
作者
VANE, JR
BOTTING, RM
机构
[1] William Harvey Research Institute, St. Bartholomew's, Hospital Medical College, London
关键词
D O I
10.1016/S0002-9149(99)80377-4
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Since the 1930s and the discovery by von Euler of a vasoactive, lipid-soluble substance that he erroneously assumed was generated by the prostate gland and therefore should be called ''prostaglandin,'' the family of prostaglandins has grown to some 90 substances. These lipid mediators are derived from arachidonic acid in the ''arachidonic acid cascade.'' In 1976, while looking for the enzyme that generates the unstable prostanold thromboxane A(2) from arachidonic acid, Moncada and Vane discovered prostaglandin I-2 and renamed it ''prostacyclin.'' Prostacyclin is the main product of arachidonic acid in all vascular tissues tested to date and strongly vasodilates all vascular beds studied. It is also the most potent endogenous inhibitor of platelet aggregation yet discovered, both inhibiting aggregation and dispersing existing aggregates. It acts through activation of adenylate cyclase, leading to increased levels of cyclic adenosine monophosphate. It also appears to have a ''cytoprotective'' activity, as yet not completely understood. Its effects are short-lasting, disappearing within 30 minutes of cessation of infusion. A stable, freeze-dried preparation of prostacyclin (epoprostenol) is available for administration to humans, and several analogs with therapeutically desirable characteristics are currently being clinically tested and should become commercially available soon. Clinical application of prostacyclin is bedeviled by 2 characteristics: it is pharmacologically unstable, so care must be taken in its use, and the correct dosage regimens have not yet been established.
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页码:A3 / A10
页数:8
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共 130 条
  • [1] PREVENTION OF BLOCKAGE OF PARTIALLY OBSTRUCTED CORONARY-ARTERIES WITH PROSTACYCLIN CORRELATES WITH INHIBITION OF PLATELET-AGGREGATION
    AIKEN, JW
    GORMAN, RR
    SHEBUSKI, RJ
    [J]. PROSTAGLANDINS, 1979, 17 (04): : 483 - 494
  • [2] ALTURA BM, 1983, HDB SHOCK TRAUMA
  • [3] CYTOPROTECTIVE ACTIONS OF PROSTACYCLIN DURING HYPOXIA IN THE ISOLATED PERFUSED CAT LIVER
    ARAKI, H
    LEFER, AM
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1980, 238 (02): : H176 - H181
  • [4] PROSTACYCLIN PRODUCTION BY ISOLATED ADIPOCYTES
    AXELROD, L
    LEVINE, L
    [J]. DIABETES, 1981, 30 (02) : 163 - 167
  • [5] BAYER BL, 1979, BRIT J PHARMACOL, V66, P10, DOI 10.1111/j.1476-5381.1979.tb16090.x
  • [6] BIPHASIC RESPONSE OF INTIMAL PROSTACYCLIN PRODUCTION DURING THE DEVELOPMENT OF EXPERIMENTAL ATHEROSCLEROSIS
    BEETENS, JR
    COENE, MC
    VERHEYEN, A
    ZONNEKEYN, L
    HERMAN, AG
    [J]. PROSTAGLANDINS, 1986, 32 (03): : 319 - 334
  • [7] BELCH JJF, 1983, LANCET, V1, P313
  • [8] BELCH JJF, 1981, THROMB HAEMOSTASIS, V42, P255
  • [9] BELCH JJF, 1993, THERAPEUTIC APPLICAT, P219
  • [10] BENNETT JG, 1981, CLIN PHARM PROSTACYC, P201