The Effect of Sumatriptan on Brain Monoamines in Rats

Abstract

Clinical data suggests that sumatriptan is effective in the acute treatment of migraine. The vascular effects of the drug have been invoked to explain this antimigraine efficacy. However, the effect of sumatriptan on brain monoamines has not previously been investigated. In order to study these hypothetical effects, we administered the drug to 24 male rats, subcutaneously, at three doses (0.3, 0.6, and 0.9 mg/kg of body weight), and 30 minutes later, all animals were decapitated. Dopamine, serotonin, and their metabolites 3,4 dihydroxyphenylacetic acid, 5-hydroxyindoleacetic acid, and homovanillic acid concentrations were measured in the frontal cortex, hypothalamus, striatum, and hippocampus, by high performance liquid chromatography. Plasma concentrations of the drug were also determined. The control group was treated with NaCl 0.9%, given subcutaneously. Sumatriptan, at the dose of 0.3 mg/kg did not alter the brain monoamine concentrations; however, at the dose of 0.6 mg/kg, sumatriptan decreased serotonin concentration in the hypothalamus and increased the turnover of dopamine and serotonin in the hypothalamus and striatum, while at the dose of 0.9 mg/kg, it augmented only the turnover of serotonin in the hypothalamus. No dose-dependent effect of the drug was found. This subcortical antidopaminergic and antiserotoninergic effect of sumatriptan may be involved in its antimigraine action.

Increased activity of serotonin uptake in platelets in medication overuse headache following regular intake of analgesics and triptans

“…As observed in different experimental conditions, triptan-sensitive 5HT 1B/1D receptors are predominantly terminal autoreceptors inhibiting 5HT release and/or synthesis and decreasing brain 5HT level [14, 15]. Acute, systemic application of sumatriptan and zolmitriptan in rats was found to decrease the 5HT synthesis in many brain regions, including the dorsal raphe nucleus.…”

Serotonin-Induced Increases in Adult Cell Proliferation and Neurogenesis are Mediated Through Different and Common 5-HT Receptor Subtypes in the Dentate Gyrus and the Subventricular Zone

“…Again, rats were injected with saline, agonist, or antagonist 4 h before killing. The doses of the serotonergic drugs used were determined based on the appropriate literature reports, specifically: 8-OH-DPAT, Owens et al (1990); sumatriptan, Mitsikostas et al (1996); GR 127935, Skingle et al (1996); DOI, Vaidya et al (1997); ketanserin, Semont et al (2000); RO 600175, Dekeyne et al (1999); SB 206553, Kennett et al (1996).…”

Sumatriptan reduces exercise capacity in healthy males: a peripheral effect of 5-hydroxytryptamine agonism?

“…In that study, rats given high subcutaneous doses of sumatriptan (0n6 mg\kg) demonstrated reduced hypothalamic concentrations of 5-HT and increased turnover of both dopamine and 5-HT. Although this dose is very high compared with that used in the treatment of migraine (approximately 0n08 mg\kg), the plasma concentration achieved (70 ng\ml) was similar to that seen in humans after a single 6 mg subcutaneous injection (72n4 ng\ml) [30,31]. Whether such an effect would be seen in humans is debatable, and impractical to confirm given our current inability to measure brain levels of neurotransmitters without invasive procedures.…”

“…Sumatriptan has also been shown to have neurogenic blocking properties in animal models, reducing trigeminal ganglion activation in response to chemical stimulation [29]. It is possible, due to the central connections to the trigeminal nucleus caudalis in the medulla oblongata, that subcortical levels of monoamines may be affected, as has been shown in rats [30]. In that study, rats given high subcutaneous doses of sumatriptan (0n6 mg\kg) demonstrated reduced hypothalamic concentrations of 5-HT and increased turnover of both dopamine and 5-HT.…”