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Chemical Compound Review:

Donitriptan 4-[4-[2-[[3-(2-aminoethyl)- 1H-indol-5...

Synonyms: CHEMBL1742428, SureCN1388876, LS-193882, AC1L53VE, L000746, ...

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Disease relevance of Donitriptan

Sumatriptan and donitriptan inhibited CGRP release as well as neurogenic inflammation [1].
We investigated the contractile effects of donitriptan and sumatriptan on human isolated blood vessels of relevance to therapeutic efficacy in migraine (middle meningeal artery) and coronary adverse events (coronary artery) [2].

High impact information on Donitriptan

Donitriptan, but not sumatriptan, inhibits capsaicin-induced canine external carotid vasodilatation via 5-HT1B rather than 5-HT1D receptors [3].
This study investigated the effects of the agonists sumatriptan (5-HT(1B/1D) water-soluble), donitriptan (5-HT(1B/1D) lipid-soluble), PNU-142633 (5-HT(1D) water-soluble) and PNU-109291 (5-HT(1D) lipid-soluble) on vasodilator responses to capsaicin, alpha-CGRP and acetylcholine in dog external carotid artery [3].
CONCLUSIONS AND IMPLICATIONS: Our results suggest that the inhibition produced by donitriptan of capsaicin-induced external carotid vasodilatation is mainly mediated by 5-HT(1B), rather than 5-HT(1D), receptors, probably by a central mechanism [3].
Donitriptan decreases jugular venous oxygen saturation in rats in the absence of cranial vasoconstriction: an overlooked mechanism of antimigraine action [4]?
The results demonstrate that donitriptan increases cerebral oxygen consumption by 5-HT(1B/1D) receptor activation in the absence of cranial vasoconstriction [4].

Biological context of Donitriptan

Effects of donitriptan on carotid haemodynamics and cardiac output distribution in anaesthetized pigs [5].
Regional blood flows were evaluated in the presence of donitriptan (10 microg/kg; n = 6) or vehicle (n = 6) [4].
Donitriptan decreased markedly and dose dependently jugular venous oxygen saturation [ED(50) 0.5 (0.3-1.1) microg/kg], in parallel with increases in carotid vascular resistance [ED(50) 0.9 (0.7-1.1) microg/kg] [6].
In addition, donitriptan was devoid of significant effects on systemic arterial pressure, heart rate, or regional blood flows, including systemic arterial-jugular venous anastomotic, systemic, or cranial [4].

Anatomical context of Donitriptan

These results show that donitriptan selectively constricts arteriovenous anastomoses via 5-HT1B receptor activation [5].
Donitriptan did not decrease vascular conductances in or blood flow to a number of organs, including the heart and kidneys; in fact, vascular conductances in the skin, brain and skeletal muscles increased [5].
Furthermore, using the concentration-response curves in the middle meningeal artery, we predicted the plasma concentration needed for the therapeutic effect of donitriptan [2].

Gene context of Donitriptan

Pierre Fabre is developing donitriptan, a piperazide 5-HT1D agonist, as a potential treatment for migraine [175854] [7].

References

An in vivo rat model to study calcitonin gene related peptide release following activation of the trigeminal vascular system. Limmroth, V., Katsarava, Z., Liedert, B., Guehring, H., Schmitz, K., Diener, H.C., Michel, M.C. Pain (2001) [Pubmed]
Comparison of contractile responses to donitriptan and sumatriptan in the human middle meningeal and coronary arteries. van den Broek, R.W., MaassenVanDenBrink, A., Mulder, P.G., Bogers, A.J., Avezaat, C.J., John, G.W., Saxena, P.R. Eur. J. Pharmacol. (2002) [Pubmed]
Donitriptan, but not sumatriptan, inhibits capsaicin-induced canine external carotid vasodilatation via 5-HT1B rather than 5-HT1D receptors. Muñoz-Islas, E., Gupta, S., Jiménez-Mena, L.R., Lozano-Cuenca, J., Sánchez-López, A., Centurión, D., Mehrotra, S., MaassenVanDenBrink, A., Villalón, C.M. Br. J. Pharmacol. (2006) [Pubmed]
Donitriptan decreases jugular venous oxygen saturation in rats in the absence of cranial vasoconstriction: an overlooked mechanism of antimigraine action? Létienne, R., Blanchet, J.C., Sole, E., John, G.W., Le Grand, B. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
Effects of donitriptan on carotid haemodynamics and cardiac output distribution in anaesthetized pigs. Tom, B., De Vries, P., Heiligers, J.P., Willems, E.W., Kapoor, K., John, G.W., Saxena, P.R. Cephalalgia : an international journal of headache. (2002) [Pubmed]
Donitriptan selectively decreases jugular venous oxygen saturation in the anesthetized pig: further insights into its mechanism of action relevant to headache relief. Letienne, R., Verscheure, Y., Perez, M., Le Grand, B., Colpaert, F.C., John, G.W. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
Donitriptan (Pierre Fabre). Dukat, M. Current opinion in investigational drugs (London, England : 2000) (2001) [Pubmed]

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