Anticoagulatory Role of an Ergot Mesylate: Hydergine
Thrombosis can be life threatening, necessitating therefore its instant treatment. Hydergine, a nootropic agent is used as a cognition enhancer in stroke patients but relatively little is known about its anti-thrombolytic effect. To investigate this aspect, in vivo and ex vivo experiments were designed and conducted. Three groups of rats were injected 1.5mg, 3.0mg and 4.5mg hydergine intraperitonealy with and without prior exposure to fresh plasma. Positive and negative controls were run in parallel. Animals were sacrificed after 1.5hrs and BT, CT, PT, INR, APTT, plasma calcium levels were estimated. For ex vivo analyses, each 1ml blood aspirated was exposed to 0.1mg, 0.2mg, 0.3mg dose of hydergine with parallel controls. Parameters analyzed were as above. Statistical analysis was through one-way ANOVA. Dunken-s and Tukey-s tests provided intra-group variance. BT, CT, PT, INR and APTT increased while calcium levels dropped significantly (P<0.05). Ex vivo, CT, PT and APTT were elevated while plasma calcium levels lowered significantly (P<0.05). Our study suggests that hydergine may act as a thrombolytic agent but warrants further studies to elucidate this role of ergot mesylates.
[1] K. Andreas,. Efficacy of cerebroprotective substances in the
management of functional disorders induced by the cytotoxic brain
edema-producing substance hexachlorophene. Nauyn-Schiedeberg's
Arch. Pharm. 1993, 347: 79-83.
[2] H. Eckert, J. KiecheL, J. Rosenthaler, R. Schmidt, and E. Schreier.
Biopharmaceutical aspects. Handbook of experimental pharmacology:
Ergot Alkaloids and Related Compounds. Berlin. Springer-Verlag. 2000,
pp: 719-803.
[3] H.F. Schran, S. McDonald, and R. Lehr. Pharmacokinetics and
bioavailability of ergoloid mesylates. Biopharm. Drug. Symp. 1988. 9:
349-361.
[4] D. Amenta, F. Ferrante and F. Franch. Effects of long-term hydergine
administration on lipofuscin accumulation in senescent rat brain.
Gerontol.1988. 34: 250-256.
[5] D.B. Rao, and J.R. Norris. A double-blind investigation of hydergine in
the treatment of cerebrovascular insufficiency in the elderly. Johns.
Hopkins. Med. J. 1971.130: 317-323.
[6] G. Steurer, P. Fitscha, K. Ettl and H. Sinzinger. Effects of hydergine on
platelet deposition on active human carotid artery lesions and platelet
function. Thromb. Res. 1989.155: 577-589.
[7] H. Sinzinger. Double blind study of the influence of co-dergocrine on
platelet parameters in healthy volunteers. Eur. J. Clini. Pharmcol., 1985.
28: 713-716.
[8] M.B. Martin. Stroke: Antithrombin versus antiplatelet therapy. J. Expert.
Opin. Inv. Drugs. 2000. 9: 355-369.
[9] M.B. Shannon and I.W. Jeffery. New anticoagulants: beyond heparin,
low molecular weight heparin and warfarin. B. J. Pharmacol. 2005.144:
1017-1028.
[10] P. Christopher, D. Joseph, A. George, M. Shahid, R. Rabekah, Q.
George, S. Elizbeth, P. William, and A. Bruce. Antidote-medicated
control of an anticoagulant aptamer in vivo. Nature Biotech. 2004. 22:
1423-1428.
[11] M. Wilhelmi, U. Frankle, T. Cohnert, P. Weber, J. Kaukemuller and S.
Fishcher. Coronary artery bypass grafting surgery without the routine
application of blood products: is it feasible? Euro. J. Cardiothoracic.
Surg. 2001.19: 657-661.
[12] C.C. Chen, J.Y. You and L.H. Ho. The APTT assay as a monitor of
heparin anticoagulation efficacy in clinical settings. Adv. Ther. 2003.20:
231-236.
[13] J. Himber, D. Kirchhofer, M. Riederer, T. Tschopp, B. Steiner and
S.P.Roux. Dissociation of antithrombotic effect and bleeding time
prolongation in rabbit by inhibiting tissue factor function. Thromb.
Haemotol. 1997.78: 1142-1149.
[14] K.J. G. Chung and M. McCusker. Effect of ginkolide mixture (BN
52063) in antagonizing skin and platelet responses to platelet
activating factor in man. Lancet. 1987. 1:248-251.
[15] L.M. Schmidt. Herbal remedies; the other drugs your patient take. Home
Health Care Nurse. 2004.22: 169-175.
[16] S. Ramstrom. Clotting time analysis of citrated blood samples is
strongly affected by the tube used for blood sampling. Blood. Coagul.
Fibrinolysis. 2005.16: 447-452.
[1] K. Andreas,. Efficacy of cerebroprotective substances in the
management of functional disorders induced by the cytotoxic brain
edema-producing substance hexachlorophene. Nauyn-Schiedeberg's
Arch. Pharm. 1993, 347: 79-83.
[2] H. Eckert, J. KiecheL, J. Rosenthaler, R. Schmidt, and E. Schreier.
Biopharmaceutical aspects. Handbook of experimental pharmacology:
Ergot Alkaloids and Related Compounds. Berlin. Springer-Verlag. 2000,
pp: 719-803.
[3] H.F. Schran, S. McDonald, and R. Lehr. Pharmacokinetics and
bioavailability of ergoloid mesylates. Biopharm. Drug. Symp. 1988. 9:
349-361.
[4] D. Amenta, F. Ferrante and F. Franch. Effects of long-term hydergine
administration on lipofuscin accumulation in senescent rat brain.
Gerontol.1988. 34: 250-256.
[5] D.B. Rao, and J.R. Norris. A double-blind investigation of hydergine in
the treatment of cerebrovascular insufficiency in the elderly. Johns.
Hopkins. Med. J. 1971.130: 317-323.
[6] G. Steurer, P. Fitscha, K. Ettl and H. Sinzinger. Effects of hydergine on
platelet deposition on active human carotid artery lesions and platelet
function. Thromb. Res. 1989.155: 577-589.
[7] H. Sinzinger. Double blind study of the influence of co-dergocrine on
platelet parameters in healthy volunteers. Eur. J. Clini. Pharmcol., 1985.
28: 713-716.
[8] M.B. Martin. Stroke: Antithrombin versus antiplatelet therapy. J. Expert.
Opin. Inv. Drugs. 2000. 9: 355-369.
[9] M.B. Shannon and I.W. Jeffery. New anticoagulants: beyond heparin,
low molecular weight heparin and warfarin. B. J. Pharmacol. 2005.144:
1017-1028.
[10] P. Christopher, D. Joseph, A. George, M. Shahid, R. Rabekah, Q.
George, S. Elizbeth, P. William, and A. Bruce. Antidote-medicated
control of an anticoagulant aptamer in vivo. Nature Biotech. 2004. 22:
1423-1428.
[11] M. Wilhelmi, U. Frankle, T. Cohnert, P. Weber, J. Kaukemuller and S.
Fishcher. Coronary artery bypass grafting surgery without the routine
application of blood products: is it feasible? Euro. J. Cardiothoracic.
Surg. 2001.19: 657-661.
[12] C.C. Chen, J.Y. You and L.H. Ho. The APTT assay as a monitor of
heparin anticoagulation efficacy in clinical settings. Adv. Ther. 2003.20:
231-236.
[13] J. Himber, D. Kirchhofer, M. Riederer, T. Tschopp, B. Steiner and
S.P.Roux. Dissociation of antithrombotic effect and bleeding time
prolongation in rabbit by inhibiting tissue factor function. Thromb.
Haemotol. 1997.78: 1142-1149.
[14] K.J. G. Chung and M. McCusker. Effect of ginkolide mixture (BN
52063) in antagonizing skin and platelet responses to platelet
activating factor in man. Lancet. 1987. 1:248-251.
[15] L.M. Schmidt. Herbal remedies; the other drugs your patient take. Home
Health Care Nurse. 2004.22: 169-175.
[16] S. Ramstrom. Clotting time analysis of citrated blood samples is
strongly affected by the tube used for blood sampling. Blood. Coagul.
Fibrinolysis. 2005.16: 447-452.
@article{"International Journal of Biological, Life and Agricultural Sciences:50399", author = "Fareeha A. and Irfan Z Qureshi", title = "Anticoagulatory Role of an Ergot Mesylate: Hydergine", abstract = "Thrombosis can be life threatening, necessitating therefore its instant treatment. Hydergine, a nootropic agent is used as a cognition enhancer in stroke patients but relatively little is known about its anti-thrombolytic effect. To investigate this aspect, in vivo and ex vivo experiments were designed and conducted. Three groups of rats were injected 1.5mg, 3.0mg and 4.5mg hydergine intraperitonealy with and without prior exposure to fresh plasma. Positive and negative controls were run in parallel. Animals were sacrificed after 1.5hrs and BT, CT, PT, INR, APTT, plasma calcium levels were estimated. For ex vivo analyses, each 1ml blood aspirated was exposed to 0.1mg, 0.2mg, 0.3mg dose of hydergine with parallel controls. Parameters analyzed were as above. Statistical analysis was through one-way ANOVA. Dunken-s and Tukey-s tests provided intra-group variance. BT, CT, PT, INR and APTT increased while calcium levels dropped significantly (P", keywords = "Hydergine, Coagulation assays, plasma calcium,
ergot mesylates, thrombosis.", volume = "5", number = "1", pages = "1-4", }
