Fenfluramine Headache

Abstract

SYNOPSIS Drug acting on brain monoamines (5HT) were tested on EH sufferers. Fenfluramine, an anorectic agent, acts principally on brain 5HT. This drug, when given to EH sufferers, precipitates and aggravates pain. The headache provoked by fenfluramine is tachyphylactic, suggesting involvement of central transmitters. Therapeutic doses of fenfluramine do not affect blood vessel diameter. This further supports a biochemical mechanism for fenfluramine headache. A reversible systemic pain syndrome has been observed in two EH sufferers, treated chronically with fenfluramine. This syndrome appears indistinguishable from that previously observed in EH sufferers, given parachlorophenylalanine, an inhibitor of 5HT synthesis. The effect of fenfluramine supports the hypothesis that established and other experimental anti‐migraine drugs act centrally by correcting abnormalities in the 5HT nociceptive system.

Drug interactions and risks associated with the use of triptans, ditans and monoclonal antibodies in migraine

“…Reversing these pulsations’ amplitude would also lead to a decrease of the headache intensity [11,12]. The role of the serotonergic neurotransmitter system herein has been confirmed by a large body of evidence [13–17].…”

Neurogenic Dural Protein Extravasation Induced by Meta-Chlorophenylpiperazine (Mcpp) Involves Nitric Oxide and 5-HT2B Receptor Activation

“…These data also provide insight into the role of serotonin, the 5‐HT 2 family of receptors and NO in dural extravasation and possibly the initiation of migraine attacks. Compounds such as reserpine and fenfluramine that cause the release of serotonin from platelets and other stores also induced migraine‐like headaches in migraineurs (25–27). Previous studies have found a correlation between functional activity of compounds at the 5‐HT 2B and 5‐HT 2C receptor subtypes and their active doses for prophylactic clinical treatment of migraine attacks (8).…”

Serotonergic mechanisms in the migraine brain – a systematic review

“…Supporting the theory of an increase in serotonin contributing to the headache are studies showing that treatment with serotonergic agonists acting on the cerebral excitatory 5-HT 2B and 5-HT 2C receptors or agents increasing synaptic serotonin causes headache (17,68,69). In contrast, intravenous infusion of serotonin relieved the pain in migraine patients (70) and inhibited sensory inputs from the dural vasculature in animals (71).…”