Effect of Ergotamine on Headache and Migraine Attack Induced by Sindenafil Citrate

Rayka Sharifian, Ayoub Barzgarnejad, Fatemeh Ghanbarpour, Mehrdad Taghipour


Sildenafil citrate is a potent vasodilatation agent to treat male erectile dysfunction and pulmonary hypertension. Among its adverse effects, headache and migraine attack have been widely reported. Here we focus on the effect of sildenafil, a selective inhibitor of CGMP hydrolyzing phosphodiesterase-5 (PDE-5), on headache induction. PDEs are large families of enzyme that break down cyclic nucleotides CGMP. When PDEs are inhibited, the levels of CGMP increase within vascular smooth muscle cells resulting in relaxation and vasodilatation in peripheral and cerebral vessels. This mechanism leads to headache. Many methods have been tried to treat headache including a pharmacological and nonpharmacological managements. In this paper, we hypothesize that ergotamine can be used to reduce the headache and migraine attack induced by sildenafil. Undoubtedly, the most important and conspicuous pharmacological effect of ergotamine is its vasoconstrictor action. This mechanism of ergot is in contrast with vasodilator action of sildenafil that can remit headache and migraine attack.

Keywords: Sildenafil; headache; migraine; Ergotamine

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Lassen LH, Ashina M, Christiansen I, Ulrich V, Grover R, Donaldson J et al. Nitric oxide synthesis inhibition: a new principle in the treatment of migraine attack. Cephalalgia 1998; 18:27-32.

Lassen LH, Haderslev PA, Jacobsen VB, Iversen HK, Sperling B, Olesen J. CGRP may play a causative role in migraine. Cephalalgia 2002; 22:54-61

Thomsen LL, Olsen J. Nitric oxide in primary headaches. Curr Opin Neurol 2001; 14:315-21.

Kruuse C, Thomsen LL, Birk S, Olsen J. Migraine can be induced by sindenafil without changes in middle cerebral artery diameter. Brain 2003; 126:241-7.

Kruuse C, Thomsen LL, Jacobsen TB, Olesen J. The phosphodiesterase 5 inhibitor sildenafil has no effect on cerebral blood flow or blood velocity, but nevertheless induces headache in healthy subjects. J Cereb Blood Flow Metab 2002; 22:1124-31

Headache Classification Subcommitee of the International Headache Society. The International Classification of Headache Disorders, 2nd edition. Cephalalgia 2004; 24(suppl. 1): 9-160.

Graham Jackson, MD, Nigel Benjamin,MD,Nevile Jackson,MD,and Michael J.Allen,MD,Effects of Sildenafil Citrate on Human Hemodynamics.Am J Cardiol 1999;83 : 13C-20C

Raybalkin SD, Yan C, Bornfeldt KE, et al. cyclic GMP phosphodiesterases and regulation of smooth muscle function. Circ Res.2003; 93:230-291.

H.A. Ghofrani, I.H.Osterloh,F.Grimminger. Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond, Nat. Rev.Drug Discov. 5 (2005) 689-702

Anna Caretti a, Monica Fantacci a, Dario Caccia b, Michele Perrella . Kenneth C.Llowe c, Michele Samaja. Modulation of the NO/cGMP pathway reduces the vasoconstriction induced by a cellular and PEGylated haemoglobin, Biochimia et Biophysia Acta 1784 (2008) 1428-1434

Goldstein H, Lue TF, Padma-Nathan H, Rosen RC, Steers WD, Wicker PA. Oral sildenafil in the treatment of erectile dysfunction. N Engl J Med 1998;338:1397-1404

Morales A, Gingell C, Collins M, Wicker PA, Osterloh IH. Clinical safety of oral sildenafil citrate(VIAGRA) in the treatment of erectile dysfunction. Int J Impot Res 1998:10:69-74.

J. J. Ibraheem, L. Paalzow, P. Tfelt-Hansen. Kinetics of ergotamine after intravenous and intramuscular administration to migraine sufferers. Euro J Clinic Pharma 1982; 23:3: 235-240

Joanne Moore. Ergotamine. University of Oklahama, College of Med, Oklahama City, USA. Elsevier Inc. 2007


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