The effect of ergotamine and dihydroergotamine on cerebral blood flow in man.

Abstract

The effects of ergotamine and dihydroergotamine on cerebral blood now was investigated 4 hours after i.v. injection as these drugs might be of importance for migraine treatment. Eight normal male volunteers (not suffering from migraine) received 0.5 mg ergotamine and 1 mg dihydroergotamine i.v. Cerebral blood flow was measured by the xenon-133 inhalation method and single-photon-emission computerized tomography before and after intravenous acetazolamide administration (1 g). Cerebral blood flow was measured before and 4 hours after ergotamine and dihydroergotamine administration. Strain-gauge measurements of toe-arm systolic gradients were used to monitor the effect of the drug on leg arteries. Mean hemispheric and regional cerebral blood flow was unchanged after either drug (mean ± SEM, ml/100 g/min): for ergotamine, 57 ± 3 before and 57 ± 3 at 4 hours; for dihydroergotamine, 54 ± 2 before and 55 ± 2 at 4 hours. The acetazolamide response was unchanged as well. Only ergotamine decreased the toe-arm systolic gradient significantly (22 mm Hg at maximum after 240 minutes; p<0.02). Thus, our study did not support the belief that ergot alkaloids should be withheld from patients during attacks of classic migraine, but this has to be investigated further. The discrepancy in the peripheral effects of ergotamine and dihydroergotamine might also be of clinical Importance. (Stroke 1987;18:120-123) T HE USE of ergotamine (E) in the treatment of classic migraine, where transient neurological symptoms form part of the attack, has been controversial for a long time since it was feared that E, a potent constrictor of peripheral arteries, might also increase the risk of ischemia by an effect on the cerebral vasculature and induce permanent neurological symptoms. E is in fact a potent vasoconstrictor of human basilar arteries in vitro, 1 and a lowering of regional cerebellar blood flow in vivo has been reported.2 Serious cases of reversible cerebral arteriopathy with segmental stenosis and even completed strokes have been reported after E was administered in inappropriately high doses.3 On the other hand, many patients have been treated with E during classic migraine attacks without any serious cerebrovascular side effects.The controversy of whether to treat classic migraine attacks by E or not was apparently solved when Hachinski et al* demonstrated that intramuscular injection of 0.2-1.0 mg ergotamine tartrate did not change cerebral blood flow (CBF) in 16 subjects when measured before and 15-20 minutes after drug administration. At this time, soon after injection, E has a pressor effect -an effect on the arterioles -but only a minor vasoconstrictory effect on the arteries per se.* Before concluding that E has no effect on CBF, the problem should be reinvestigated at a time when the effect on arteries should be maximal, i.e., 4-6 hours after administration of E.6 An alternative to E in classicFrom the

Carotid vascular effects of ergotamine and dihydroergotamine in the pig: no exclusive mediation via 5‐HT1‐like receptors

“…It is interesting to note that, despite an increase in vascular conductance in several cranial extracerebral tissues and the nutrient conductance as a whole, dural vascular conductance decreased with the ergots. There was no effect on the cerebral component of the carotid blood flow in our experiments, which is in keeping with the observations in both animals and man that total cerebral blood flow is little affected by ergotamine and dihydroergotamine (Hatchinski et al, 1978;Johnston & Saxena, 1978;Andersen et al, 1987). Pretreatment with 3mgkg-' methiothepin partly antagonized the effects of the two ergot alkaloids.…”

Clinical Comparative Study of Sumatriptan Versus Ergotamine Therapy in Migraine

“…India spent the least amount on health care; the government of India spent less than 2% GDP on health. 10,11,12,13 This is lesser than sub-Saharan countries. Hence, conventional ergotamine therapy can be made available in government hospital and physician in general hospital can continue to prescribe the conventional therapy rather the sumatriptan.…”

“…8,9,10 Magnesium Deficiency Another theory proposes that deficiency of magnesium in brain triggers a chain of events starting with platelet aggression resulting in release of 5-HT, which is a vasoconstrictor. 11,12,13 Endothelial Dysfunction Nitric oxide released by microglial is a potentially cytotoxic proinflammatory mediator initiating and maintaining brain inflammation. 13,14,15 Serotonin and Migraine Serotonin receptors are believed to be the most important receptor in the headache pathway.…”

The serotonergic system in migraine

“…However they do not seem to have any effect on blood flow through the cerebral hemispheres [12] and this suggests their efficacy in migraine may be independent of their vasoconstrictive effect.…”