Agonist activity of antimigraine drugs at recombinant human 5-HT1A receptors: potential implications for prophylactic and acute therapy

  title={Agonist activity of antimigraine drugs at recombinant human 5-HT1A receptors: potential implications for prophylactic and acute therapy},
  author={Adrian Newman-Tancredi and Caroline Conte and Christine Chaput and Laurence Verri{\`e}le and V. Audinot-Bouchez and Sylvia Lochon and Gilbert Lavielle and Mark J. Millan},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
The actions of several serotonergic ligands in use or under development for the treatment of migraine headaches were examined at recombinant human 5-HT1A receptors stably expressed in Chinese Hamster Ovary cells. Affinities (Kis) at this site were determined in competition binding experiments with [3H]-8-OH-DPAT ([3H](±)8-hydroxy-N,N-dipropylaminotetralin), whilst agonist efficacy was measured by stimulation of [35S]-GTPγS (guanylyl-5’-[γ[35S]thio]-triphosphate) binding. Of the prophylactic… 

Activation of 5-hydroxytryptamine1B/1D/1F receptors as a mechanism of action of antimigraine drugs

Although the triptans are very effective in treating migraine attacks, their shortcomings have stimulated the search for novel drugs, and the focus is on 5-HT1F receptor agonists, which seem devoid of vascular side effects.

Dimerization of 8-OH-DPAT increases activity at serotonin 5-HT1A receptors

The differential regulation of the maximal agonist responses by GDP suggests that the [35S]GTPγS binding responses to these two ligands could be mediated by different G-protein subtypes upon activation of the 5-HT1A receptor.

Interaction of 5-HT1B/D ligands with recombinant h 5-HT1A receptors:Intrinsic activity and modulation by G-protein activation state

The differential regulation of 5-HT1A and 5- HT1B/D agonist responses by GDP suggests that different G-protein subtypes are involved upon 5-ht1A receptor activation by 5-hydroergotamine and5-HT2A receptors, and increasing the amount of GDP with C6-glial membranes results in an attenuation of both the agonist’s maximal effect and the apparent potency of partial agonists.

Chronic 5-HT2 receptor blockade unmasks the role of 5-HT1F receptors in the inhibition of rat cardioaccelerator sympathetic outflow.

The results confirm the cardiac sympatho-inhibitory role of 5-HT1B, 5- HT1D, and5-HT5A receptors in both groups; nevertheless, sarpogrelate treatment specifically unmasked a cardiac sympathO-inhibition mediated by 5-ht1F receptors.

5-Hydroxytryptamine receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Unique amongst the GPCRs, RNA editing produces 5-HT2C receptor isoforms that differ in function, such as efficiency and specificity of coupling to Gq/11 and also pharmacology [40, 482].

Pharmacological analysis of the haemodynamic effects of 5‐HT1B/D receptor agonists in the normotensive rat

The receptors involved in mediating the haemodynamic effects of three 5‐HT1B/D receptor agonists were investigated in pentobarbitone anaesthetized rats and rizatriptan failed to induce hypotension or bradycardia in pithed rats with MAP normalized by angiotensin II.

Cardiovascular toxicity of novel psychoactive drugs: Lessons from the past

Naratriptan Has a Selective Inhibitory Effect on Trigeminovascular Neurones at Central 5-HT1A and 5-HT1B/1D Receptors in the Cat: Implications for Migraine Therapy

Results indicate that naratriptan has a central effect in the trigeminovascular system, selectively inhibiting afferent activity in craniovascular neurones, via both 5-HT1B/1D and 5- HT1A receptors.



Is migraine prophylactic activity caused by 5-HT2B or 5-HT2C receptor blockade?

GR127935: a potent and selective 5-HT1D receptor antagonist

High-level stable expression of recombinant 5-HT1A 5-hydroxytryptamine receptors in Chinese hamster ovary cells.

A series of 5-hydroxytryptamine agonists inhibited forskolin-stimulated adenylate cyclase activity in the cells and, despite the high level of receptor expression, their apparent efficacies were similar to those observed for inhibition ofAdenylates cyclase in brain.

Pharmacological characterisation of [35S]-GTPgammaS binding to Chinese hamster ovary cell membranes stably expressing cloned human 5-HT1D receptor subtypes.

The data show that [35S]-GTPgammaS binding is a suitable method for studying the interaction between cloned human 5-HT1D receptors and G-proteins.

Potency of 5-hydroxytryptamine1a agonists to inhibit adenylyl cyclase activity is a function of affinity for the "low-affinity" state of [3H]8-hydroxy-N,N-dipropylaminotetralin ([3H]8-OH-DPAT) binding.

In this study, the radiolabeled 5-hydroxytryptamine1A agonist, [3H]8-hydroxy-N,N-dipropylamino tetralin ([3H]8-OH-DPAT), was shown to have both a high (Kd, 0.7 +/- 0.2 nM) and a low (Kd, 17 +/- 4 nM)

The 5-HT1Dreceptor antagonist GR 127,935 is an agonist at cloned human 5-HT1Dα receptor sites

International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin).

It is evident that in the last decade or so, a vast amount of new information has become available concerning the various 5-HT receptor types and their characteristics, and it is important to rationalise in concert all of the available data from studies involving both operational approaches of the classical pharmacological type and those from molecular and cellular biology.