Effect of serotonin in migraine patients

Abstract

LITTLE is known of the factors that predispose to migraine or the biochemical events that initiate the disturbances characteristic of this condition. Earlier studies by Marcussen and Wolffl have shown that an initial phase of vasoconstriction is responsible for the prodroma1 symptoms, while the pain follows a marked distention of cranial vessels that are temporarily hypotonic. They also have presented certain evidence which presumably indicates that a pain threshold-lowering substance renders the distention of the large arteries painfu1.2 However, alteration in tone, lumen, and pain threshold of the arteries alone cannot explain the complex symptomatology of the migraine attack.Jimenez Diaz and associates3 have indicated that, during the migraine attack, there is a release of a substance more stable than acetylcholine, which they term S.A.C. acetylcholinelike substance. They also conclude that the normal choline acetylate system is different in these patients. Kunkle4 also relates this multisystem disturbance to a preponderance of parasympathetic nervous activity as manifested by a release of acetylcholine. An acetylcholine-like substance has been detected in cerebrospinal fluid during some intracranial vascular headaches of migraine type. These and other studies cast light on the nature of the pathophysiology of migraine, yet the primary event in the migraine attack remains undetermined. The effects of serotonin (5-hydroxytryptamine-HT) suggest themselves as a means of gaining further understanding of migraine.The present study undertakes to determine the effects-clinically, physiologically, and biochemically-of serotonin and its precursor, 5-hydroxytryptophane (HTP), on patients with migraine. The physiologic significance of HT is implied by its potency in the central nervous system, gastrointestinal tract, cardiovascular system, and blood. The cardiovascular phenomena associated with HT excess are particularly interesting, in that its ability to produce vasoconstriction in some instances, and in some instances vasodilation, raises the possibility that this or a similar substance is the trigger, or part of the trigger mechanism, in patients with vascular headaches, that is, migraine. The nervous, cardiovascular, gastrointestinal, and renal effects of HT all have their counterparts in the migraine syndrome. It has been stated by other observers that exogenous HT can elicit an attack of migraine,5 and observations with a monoamine oxidase inhibitor have been interpreted to indicate that HT aggravates the symptoms of migraine.s WOW and associates7 have reported that, in 3 cases, temporal perivascular-injected HT induced effects similar to clinical migraine. This and other clinical studies suggest that a biochemical lesion of fundamental importance exists in migraine. MATERIALS AND METHODSPatients used in this study were a group of 18 females and 17 males between the ages of 24 and 70, all of whom meet our previous criteria for migraines and are otherwise in good health. They were all studied at the Montefiore Hos...

Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle

“…With the first class of MAO inhibitors, uncontrolled studies, lacking a comparison, were initiated to determine whether these drugs could be of use in the treatment of migraine and tension type headaches (Dalsgaard-Neilson, 1962;Michelacci & Franchi, 1962). These studies were based on the hypothesis that these diseases are caused by low levels of serotonin in the brain which subsequently led to the development of triptans to act as agonists on the serotonin receptors (Kimball, Friedman & Vallejo, 1960;Saxena & Ferrari, 1992). Phenelzine was considered a powerful medication for migraines and daily headaches.…”

Current and prospective pharmacological targets in relation to antimigraine action

“…In this respect, (a) there is an elevation of urinary excretion of 5-hydroxyindole acetic acid, the major metabolite of 5-HT, during migraine attacks (Curran et al 1965); (b) platelet 5-HT levels were found to drop rapidly during the onset of a migraine attack (Anthony et al 1967); (c) reserpine, which depletes 5-HT (and noradrenaline), precipitates migraine attacks (Carroll and Hilton 1974); intravenous injection of 5-HT reduces headache intensity in migraineurs (Anthony et al 1967;Kimball et al 1960). …”

Nimodipine‐induced changes in the distribution of carotid blood flow and cardiac output in pentobarbitone‐anaesthetized pigs

“…Arteriovenous shunting has been implicated in the pathophysiology of migraine where profound vasodilatation in these large shunt vessels may lead to a reverse 'steal' (Heyck, 1969;Saxena, 1978;. Indeed anti-migraine drugs, particularly the ergot alkaloids effective in the treatment of individual attacks (Johnston & Saxena, 1978;Schamhardt et al, 1979;Spierings & Saxena, 1980), as well as 5-HT (Saxena & Verdouw, 1982) which may also alleviate migraine attacks (Kimball et al, 1960;Lance, 1982), cause an 'active' constriction of AVAs. Though the overall effect of nimodipine on the distribution of carotid artery blood flow into nutrient and nonnutrient fractions qualitatively resembles that of the above drugs, nimodipine is less efficacious and, as discussed above, has a 'passive' effect on AVAs.…”