Effects of 5-Hydroxytryptamine and Ergotamine on Human Superficial Temporal Artery

Abstract

Isometric tension was recorded in ring preparations of human superficial temporal arteries contracted by noradrenaline (NA), 5-hydroxytryptamine (5-HT), and ergotamine. In contrast to NA and 5-HT, ergotamine induced long-lasting contractions refractive to additional stimulations and resistant to repeated wash-out. When tested against 5-HT, ergotamine acted as a non-competitive antagonist. When repeating the 5-HT stimulations (4.7 x 10(-5) M) the contractile response decreased indicating tachyphylaxis to this agent. As ergotamine revealed both a vasoconstrictive and a 5-HT-blocking activity, the beneficial effect in migraine may be by an interference during both the vasoconstrictory and vasodilatory phases.

Kinetics of 5-HT2BReceptor Signaling: Profound Agonist-Dependent Effects on Signaling Onset and Duration

“…However, a number of ex vivo tissue studies suggest that ergots may be tightly bound to their receptor targets in a wash-resistant manner. Ergotamine and dihydroergotamine induce slow-onset, prolonged contractions of human coronary and superficial temporal arterial preparations that are resistant to compound washout (Ostergaard et al, 1981;MaassenVanDenBrink et al, 1998). Similarly, dihydroergotamineinduced contractions of canine saphenous and femoral vein strips (Muller-Schweinitzer, 1980) and ergovaline-induced contraction of rat and guinea pig arterial preparations (Schoning et al, 2001) are prolonged and resistant to washout.…”

Allodynia Is Associated With Initial and Sustained Response to Acute Migraine Treatment: Results from the American Migraine Prevalence and Prevention Study

“…17 Regarding the other drugs, opioids are usually excitatory, rather than inhibitory in the dorsal horn, 37,38 potentially by interfering with glutamate clearance from the synapse 39 ; barbiturates, which suppress neuronal firing by increasing chloride conductance through its binding to the GABA A receptor, 40 are thought to achieve their therapeutic effects mainly by increasing GABA level in supraspinal brain areas rather than in the spinal cord 41 ; and ergot alkaloids are thought to exert their anti-migraine effects by acting mainly on peripheral tissues (through 5-HT 1,2 receptors, a1and a2-adrenoceptors, and D 2 -like dopamine receptors) to prevent release of vasoactive neuropeptides and cause vasoconstriction of peripheral blood vessels. [42][43][44][45][46][47][48] The peripheral activity of ergot alkaloids, as well as their being the only migraine-specific medications besides triptans that were assessed, may help to explain why individuals using them did not differ from triptan users on the 2hPF outcome. This result may also be due to a potentially faster onset of intranasal and injectable forms of ergot alkaloids.…”

Dihydroergotamine: discrepancy between arterial, arteriolar and pharmacokinetic data

“…The long‐terminal half‐life of DHE and its extensive metabolism which results in the formation of active metabolites [21, 24] provide possible explanations for the prolonged vascular activity of DHE in vivo . However, these arguments cannot explain the sustained vasoconstrictor activity of ergot alkaloids in vitro which persists even after repeated washing [9, 10]. Therefore, as is suggested by the large volume of distribution, tight tissue binding resulting in slow diffusion from the receptor biophase is likely to contribute substantially to these effects.…”