Effects of Chronic Sumatriptan and Zolmitriptan Treatment on 5-HT₁ Receptor Expression and Function in Rats

Abstract

Triptans are commonly used anti-migraine drugs and show agonist action mainly at serotonin 5-HT(1B/1D/1F) receptors. It is not known whether frequent or long-term treatment with these drugs would alter 5-HT receptor function. We investigated the effects of protracted (14-18 days) sumatriptan and zolmitriptan treatment in rats on 5-HT(1) receptor mRNA expression and function in tissues related to migraine pathophysiology. RT-PCR analysis revealed that 5-HT(1B/1D/1F) receptor mRNA was reduced in the trigeminal ganglion after treatment with either triptan (reduction by: sumatriptan 39% and zolmitriptan 61% for 5-HT(1B); 60%vs 41% for 5-HT(1D); 32%vs 68% for 5-HT(1F)). Sumatriptan attenuated 5-HT(1D) receptor mRNA by 49% in the basilar artery, whereas zolmitriptan reduced 5-HT(1B) mRNA in this tissue by 70%. No change in 5-HT(1) receptor mRNA expression was observed in coronary artery and dura mater. Chronic triptan treatment had no effect in two functional assays [sumatriptan mediated inhibition (50 mg/kg, i.p.) of electrically induced plasma protein extravasation in dura mater and 5-nonyloxytryptamine-stimulated [(35)S]guanosine-5'-O-(3-thio)triphosphate binding in substantia nigra]. Furthermore, vasoconstriction to 5-HT in isolated basilar artery was not affected by chronic triptan treatment, while it was slightly reduced in coronary artery. We conclude that, although our treatment protocol altered mRNA receptor expression in several tissues relevant to migraine pathophysiology, it did not attenuate 5-HT(1) receptor-dependent functions in rats.

Zolmitriptan: A Novel Portal Hypotensive Agent Which Synergizes with Propranolol in Lowering Portal Pressure

“…Our results with zolmitriptan in experimental animals are in accordance with pharmacological studies in humans where no significant changes in MAP have been described [23]. Also, previous studies indicate that sustained zolmitriptan administration does not cause tachyphylaxis [24]–[25]. In agreement with these data we observed 14% reduction of PVP in CBDL rats treated with zolmitriptan for one week.…”

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

“…Chronically applied, the drugs induced a significant increase of 5HT synthesis in many projection areas but not in the dorsal raphe nucleus [14]. Reuter et al [16] demonstrated that chronic sumatriptan and zolmitriptan treatment (2 weeks) significantly reduces 5HT 1B/1D/1F mRNA in trigeminal ganglion cells. Thus, excessive use of anti-migraine medication may result in alterations of serotonergic neurotransmission.…”

Up-regulation of calcitonin gene-related peptide in trigeminal ganglion following chronic exposure to paracetamol in a CSD migraine animal model

“…Chronic use of analgesic drugs could result in a decrease in the level of 5-HT and up-regulate the5-HT2A receptors in platelets (Srikiatkhachorn and Anthony, 1996;Srikiatkhachorn et al, 1998). Down-regulation of the 5-HT1 receptor (5-HT1B/1D) has also been demonstrated in animals receiving chronic treatment with an anti-migraine drug (Reuter et al, 2004). As mentioned above, 5-HT is a crucial pain modulator in trigeminal nociception; it plays an important role in controlling CGRP synthesis and release in TG.…”