In vitro effect of the coronary vasodilator diltiazem on human and rabbit platelets

Shinjo, Akihisa; Sasaki, Yoshiyuki; Inamasu, Masanori; Morita, Takashi

doi:10.1016/0049-3848(78)90224-4

Cited by 39 publications

(7 citation statements)

References 22 publications

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“…Nifedipine and diltiazem also have antiaggregatory activity [215], [216]. There are pronounced differences between these three blockers in their activity patterns against different types of aggregation.…”

Section: Calcium Entry Blockersmentioning

confidence: 99%

Cardiovascular Drugs

Hollmann¹,

Lehmann²,

Albrecht³

et al. 2000

Ullmann's Encyclopedia of Industrial Chemistry

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Section: Calcium Entry Blockersmentioning

confidence: 99%

Cardiovascular Drugs

Hollmann¹,

Lehmann²,

Albrecht³

et al. 2000

Ullmann's Encyclopedia of Industrial Chemistry

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“…Attempts to demonstrate slow calcium channels in plate lets have been unsuccessful [17], and there fore the predominate mechanism whereby diltiazem interacts with cardiac and vascular smooth muscle may not apply to platelets. Antagonism of platelet aggregation re sponses in vitro usually requires diltiazem concentrations (100-500 pmol/1) [1][2][3][4] that greatly exceed the therapeutic plasma levels (0.1-1 pmol/1) [18] capable of blocking cal cium channels in other tissues. Diltiazem at concentrations of 100 pmol/1 interferes with intracellular calcium mobilization [20] and also inhibits phosphodiesterase leading to increased cAMP levels [21], These two ac tions could be responsible for the interfer ence with thrombocyte activation by diltia zem.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous investigators have found that relatively high diltiazem concentrations strongly block the in vitro aggregation of platelets to ADP. col lagen, platelet-activating factor (PAF) and prostaglandin Hi or U-46,619 [1][2][3][4]. In con trast, published demonstrations of the anti-thrombotic efficacy of diltiazem in vivo have been scarce.…”

Section: Introductionmentioning

confidence: 99%

Effect of Diltiazem on Experimental Coronary Artery Thrombosis in Dogs

Schumacher

Lucchesi²

1990

Pharmacology

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The effect of the calcium channel blocker diltiazem on arterial thrombosis was determined in anesthetized dogs subjected to continuous anodal stimulation of the intimal surface of the left circumflex coronary artery (LCCA). Infusion of saline (n = 6) or diltiazem (80 µg/kg plus 20 µg/kg/min i.v.; n = 6) was begun 15min before electrical stimulation. Diltiazem prolonged the P-R interval by 28% and reduced mean arterial blood pressure (ABP) by 9%. All animals developed occlusive thrombosis. Saline- and diltiazem-treated dogs did not differ in the time to occlusion (204 ± 30 and 153 ± 27 min, respectively) and LCCA thrombus mass (25 ± 4 and 24 ± 3 mg, respectively). LCCA flows measured intermittently during thrombogenesis also did not differ between treatment groups, although the frequency of spontaneous flow increases which interrupted the flow declines was reduced 53% by diltiazem. In separate diltiazem-treated dogs (80 µg/kg plus 20 µg/kg/min i.v. for 2 h; n = 7) the ex vivo platelet aggregation response to platelet-activating factor (PAF) was inhibited (-45%), but not the response to collagen. When 5 and 25 µmol/l diltiazem was tested in vitro, again the aggregation response to PAF was reduced (-25 and -81%, respectively) while that to collagen was unaffected. These results demonstrate that diltiazem does not impede thrombus formation in vivo when given at a dose that exerts threshold hemodynamic activity and significantly impairs platelet function.

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“…This inhibitory action of diltiazem on platelets seems to operate, at least in part, through a mechanism other than calcium antagonism because /-diltiazem, a stereoisomer of dilti azem, showed almost an equally potent inhibitory effect on platelet aggregation in spite of its very weak calcium-blocking activity compared with diltiazem (3). The finding that diltiazem inhibited both ADP induced primary and secondary aggregation in human platelets at relatively high concen trations (above 10-4 M) (2) suggests that diltiazem, like many other membrane-active drugs such as chlorpromazine and propranolol (4)(5)(6)(7), may exert the inhibitory action through a modification of physicochemical properties of the platelet membrane.…”

mentioning

confidence: 99%

“…Diltiazem, a potent coronary vasodilator which acts as a calcium entry blocker (1), also inhibits platelet aggregation in vitro (2). This inhibitory action of diltiazem on platelets seems to operate, at least in part, through a mechanism other than calcium antagonism because /-diltiazem, a stereoisomer of dilti azem, showed almost an equally potent inhibitory effect on platelet aggregation in spite of its very weak calcium-blocking activity compared with diltiazem (3).…”

mentioning

confidence: 99%