Induction of migrainelike headaches by the serotonin agonist m-chlorophenylpiperazine

Abstract

In a study of serotonin (5-HT) function in patients with eating disorders and healthy control subjects, severe headaches with features of common migraine occurred unexpectedly in 28 of 52 subjects (54%) 8 to 12 hours after receiving a single oral dose of the 5-HT receptor agonist m-chlorophenylpiperazine (m-CPP), 0.5 mg/kg. None of the same subjects developed similar late-occurring headaches after placebo or the 5-HT precursor, L-tryptophan, 100 mg/kg given intravenously. The frequency of these migrainelike headaches was not significantly different between patients with bulimia or anorexia nervosa and control subjects, but incidence of headaches was significantly greater in subjects with a personal or family history of migraine, with almost all predisposed individuals (18 of 20, 90%) developing severe symptoms. Headache ratings were also significantly correlated (rho = 0.70; p less than 0.0001) with peak concentrations of m-CPP in plasma. These observations indicate that m-CPP may provide a novel probe for studies of the pathophysiology of migraine headaches.

Cross-talk between 5-Hydroxytryptamine Receptors in a Serotonergic Cell Line

“…A role has been proposed for the 5-HT2C receptor since the 5-HT2A preferential antagonist, ketanserin, is not effective (39). This assumption is further supported by the observation that the 5-HT2C agonist, mCPP, triggers migraine attacks (40). Nevertheless, only trace amounts of 5-HT2C receptor mRNA are detected in meningeal tissues.…”

Pharmacological analysis of red-wine-induced migrainous headaches

“…In a now classic paper, Brewerton et al [19] found that the trazadone metabolite metachlorophenylpiperazine (mCPP) would trigger headaches in some patients with a previous history of migraine, though it is unclear from this report whether this applies to only a proportion of migrainous subjects. There is increasing evidence that this substance has significant agonist pharmacological activity at 5HT 2 receptor sub-types, particularly as the response is blocked by the serotonin antagonist metergoline [20].…”

The serotonergic system in migraine

“…Before the characterisation of 5-HT2 subtypes, it was believed that their efficacy was due to 5-HT 2 Nevertheless, pizotifen, cyproheptadine, and methysergide are potent 5-HT 2B and 5-HT 2C receptor antagonists, while mCPP, an agonist of these, can induce migraine [13,14]. These three drugs, along with amitriptyline, propanolol, ketanserin, ritanserin, and mianserin, do not discriminate between 5-HT 2B and 5-HT 2C sites [15].…”