Triptans in clinical practice: the basic scientist’s point of view

Since the observation that sumatriptan, the first triptan to be synthetized as a specific antimigraine compound, was able to block neurogenic inflammation (NI) in intra– and extracranial rat tissues, the experimental model for NI development has been used to predict the efficacy in aborting migraine pain of other compounds with activity on 5-HT1B/1D receptors. Most of the drugs active on 5–HT1 receptors that have been tried in the NI model effectively inhibited or decreased this response, although some of them lack of clinical efficacy on migraine pain, suggesting that pain relief does not correlate with NI blockade. A central pathophysiological mechanism has been advocated since migraine attack is considered to be a discharge from a central “generator”, probably located in the brainstem. The hypothesis is supported by experimental data showing that triptans inhibit excitability of neurons in the trigeminal nucleus caudalis when locally applied. This experimental model does not rule out the involvement of peripheral blockade during migraine attack. Probably, neurophysiological studies in humans provide better information than do experimental animal models about central mechanisms of action of triptans. Receptor pharmacology is also important for understanding beneficial or undesidered side effects other than pain relief. Biochemical studies are therefore needed to better understand how triptans work and to design new abortive or preventive drugs.