PDF herunterladen
Thromb Haemost 1978; 39(01): 074-083
DOI: 10.1055/s-0038-1646657
Original Article
Schattauer GmbH Stuttgart

Effect of 1-Methyl-2-Mercapto-5-(3-Pyridyl)-Imidazole (KC-6141), an Anti-Aggregating Compound, on Experimental Thrombosis in Rats

Teruhiko Umetsu
The Central Research Laboratory, Kaken Chemical Co., Ltd., Honkomagome 2-28-8, Bunkyo-Ku, Tokyo 113, Japan
,
Kazuko Sanai
The Central Research Laboratory, Kaken Chemical Co., Ltd., Honkomagome 2-28-8, Bunkyo-Ku, Tokyo 113, Japan
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 24. Februar 1997

Accepted 24. Juli 1997

Publikationsdatum:
12. Juli 2018 (online)

Auch verfügbar auf
  als PDF herunterladen  Lizenzen und Reprints

Summary

In order to evaluate 1-methyl-2-mercapto-5-(3-pyridyl)-imidazole (KC-6141) as a possible antithrombotic compound, a simple and reproducible method for experimental thrombosis in rats was devised. A silken thread was inserted in the extracorporeal shunt between the carotid artery and the jugular vein. 15 min after the circulation of blood, wet weight of thrombus which developed on the thread was measured to determine the degree and rate of thrombus formation. Equalization of average body weight of rats for each group provided good reproducibility. Microscopic examination demonstrated that the thrombus was primarily composed of platelets.

By use of the technique, the activities of KC-6141 and two known inhibitors, aspirin and dipyridamole, were determined. Of the three compounds, KC-6141 was the most potent inhibitor for the thrombosis. Its ED50 was 60 mg/kg when given orally and the compound was active for about 40 hr. Aspirin was about twice as less active than KC-6141 and dipyridamole showed no effect on the thrombosis.

The ranking order of potency against the experimental thrombosis for the three compounds was the same as that for inhibition of platelet aggregation in vitro and platelet retention in rats, as reported previously by us. Therefore the method seems to be associated with platelet aggregation and retention.

The above result suggests that KC-6141 is of value as antithrombotic drug in vivo.

 

  • References

  • 1 Aaron RK, Srinivasan S, Burrowes CB, Sawyer PN. 1970; Effects of chemical compounds upon current induced thrombosis in rat mesentric vessels. Thrombosis et Diathesis Haemorrhagica 23: 621
    PubMedSuche in Google Scholar
  • 2 Arfors KE, Hint HC, Dhall DP, Matheson NA. 1968; Counteraction of platelet activity at sites of laser-induced endothelial trauma. British Medical Journal 4: 430
    CrossrefPubMedSuche in Google Scholar
  • 3 Baumgartner HR. 1973; The role of blood flow in platelet adhesion, fibrin deposition, and formation of mural thrombi. Micro vascular Research 5: 167
    PubMedSuche in Google Scholar
  • 4 Brecher G, Cronkite EP. 1950; Morphology and enumeration of human blood platelets. Journal of Applied Physiology 3: 365
    CrossrefPubMedSuche in Google Scholar
  • 5 Broersma RJ, Dickerson GD, Sullivan MS. 1973; The determination of platelet aggregation by filtration pressure in circulating dog blood. Thrombosis et Diathesis Haemorrhagica 29: 201
    PubMedSuche in Google Scholar
  • 6 Danses CA, Voleti CD, Weiss HJ. 1971; Protection by aspirin against experimentally induced arterial thrombosis in dogs. Thrombosis et Diathesis Haemorrhagica 25: 288
    PubMedSuche in Google Scholar
  • 7 Didisheim P. 1968; Inhibition by dipyridamole of arterial thrombosis in rats. Thrombosis et Diathesis Haemorrhagica 20: 257
    PubMedSuche in Google Scholar
  • 8 Didisheim P. 1972. Animal models useful in the study of thrombosis and antithrombotic agents. In: Spaet TH. (ed.) Progress in Hemostasis and Thrombosis. Grune and Stratton, Inc.; 165
    Suche in Google Scholar
  • 9 Didisheim P, Bowie EJW, Owen CA. 1970; Inhibition of arterial thrombosis and platelet adhesiveness in the rat by intravenous 2,4,6,-trimorpholinopyrimido-(5,4-d)-pyrimidine (RA433). Mayo Clinic Proceeding 45: 51
    PubMedSuche in Google Scholar
  • 10 Didisheim P, Owen CA. 1970; Effect of dipyridamole (Persantin®) and its derivatives on thrombosis and platelet function. Thrombosis et Diathesis Haemorrhagica Suppl 42: 267
    PubMedSuche in Google Scholar
  • 11 Downie HG, Murphy EA, Rowsell HC, Mustard JF. 1963; Extracorpreal circulation. A device for the quantitative study of thrombus formation in flowing blood. Circulation Research 12: 441
    CrossrefPubMedSuche in Google Scholar
  • 12 Emmons PR, Harrison MJG, Honour AJ, Mitchell JRA. 1965; a Effect of dipyridamole on human platelet behaviour. Lancet II: 603
    PubMedSuche in Google Scholar
  • 13 Emmons PR, Harrison MJG, Honour AJ, Mitchell JRA. 1965; b Effect of a pyrimidopyrimidine derivative on thrombus formation in the rabbit. Nature 208: 255
    CrossrefPubMedSuche in Google Scholar
  • 14 Evans G, Mustard JF. 1968; Platelet surface reaction and thrombosis. Surgery 64: 273
    PubMedSuche in Google Scholar
  • 15 Evans G, Packham MA, Nishizawa EE, Mustard JF, Murphy EA. 1968; The effect of acetylsalicylic acid on platelet function. Journal of Experimental Medicine 128: 877
    CrossrefPubMedSuche in Google Scholar
  • 16 Gray GR, Wilson PA, Douglas AS. 1968; The effect of dipyridamole on platelet aggregation and adhesiveness. Scottish Medical Journal 13: 409
    CrossrefPubMedSuche in Google Scholar
  • 17 Herrmann RG, Marshall WS, Crowe VG, Frank JD, Marlett DL, Lacefield WB. 1972; Effect of a new anti-inflammatory drug, fenoprofen, on platelet aggregation and thrombus formation. Proceedings of the Society for Experimental Biology and Medicine 139: 548
    PubMedSuche in Google Scholar
  • 18 Hirsh J, Gent M, Genton E. 1975; The current status of platelet suppressive drugs in the treatment of thrombosis. Thrombosis et Diathesis Haemorrhagica 33: 406
    PubMedSuche in Google Scholar
  • 19 Jørgensen L, Haerem JW, Moe N. 1973; Platelet thrombosis and non-traumatic intimal injury in mouse aorta. Thrombosis et Diathesis Haemorrhagica 29: 470
    PubMedSuche in Google Scholar
  • 20 Muirhead CR. 1973; The filter loop technique as a method of measuring platelet aggregation in the flowing blood of the rat. the inhibitory activity of 5-oxo-l-cyclopentene-l-hepatonic acid (AY-16,804) on platelet aggregation. Thrombosis et Diathesis Haemorrhagica 30: 138
    PubMedSuche in Google Scholar
  • 21 O’Brien JR. 1968; Effects of salicylates on human platelets. Lancet I: 779
    PubMedSuche in Google Scholar
  • 22 Spilker BA, Balken HV. 1973; Formation and embolization of thrombi after electrical stimulation. On the method and evaluation of drugs. Thrombosis et Diathesis Haemorrhagica 30: 352
    PubMedSuche in Google Scholar
  • 23 Sullivan JM, Kagnoff MF, Gorlin R. 1968; Reduction of platelet adhesiveness inpatients with coronary artery disease. American Journal of Medical Sciences 255: 292
    CrossrefPubMedSuche in Google Scholar
  • 24 Turitto VT, Baumgartner HB. 1974; Effect of physical factors on platelet adherence to subendothelium. Thrombosis et Diathesis Haemorrhagica Suppl 60: 17
    PubMedSuche in Google Scholar
  • 25 Umetsu T, Sanai K, Kato T. 1976; Effects of bupranolol, a new β-blocker, on platelet functions of rabbit and human in vitro. Thrombosis and Haemostasis 36: 316
    PubMedSuche in Google Scholar
  • 26 Umetsu T, Kato T. 1978; Effect of 1-methyl-2-mercapto-5-(3-pyridyl)-imidazole (KC-6141) on rabbit platelet aggregation in vitro and rat platelet retention. Thrombosis and Haemostasis 39: 167
    Thieme ConnectPubMedSuche in Google Scholar
  • 27 Weiss HJ, Aledort LM, Kochwa S. 1968; The effect of salicylates on the hemostatic properties of platelet in man. Journal of Clinical Investigation 47: 2169
    CrossrefPubMedSuche in Google Scholar
  • 28 Zak SB, Tallan HH, Quinn GP, Fratta I, Greengard P. 1963; The determination and physiological distribution of dipyridamole and its glucuronides in biological material. Journal of Pharmacology and Experimental Therapeutics 141: 392
    PubMedSuche in Google Scholar
  • 29 Zucker MB, Peterson J. 1970; Effect of acetylsalicylicacid, other nonsteroidal anti-inflammat-ory agents, and dipyridamole on human blood platelets. Journal of Laboratory and Clinical Medicine 76: 66
    PubMedSuche in Google Scholar