Dihydroergotamine and sumatriptan in isolated human coronary artery, middle meningeal artery and saphenous vein

Labruijere, Sieneke; Chan, Kayi Y.; Vries, René de; Bogaerdt, Antoon J. van den; Dirven, Clemens; Danser, AH Jan; Kori, Shashidhar; MaassenVanDenBrink, Antoinette

doi:10.1177/0333102414544977

Cited by 18 publications

(18 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The segments were mounted on stainless steel hooks in 15‐ml organ baths filled with oxygenated Krebs buffer solution at 37°C. After equilibration for at least 30 min and a wash every 15 min, the vessel segments were stretched to a stable tension of about 15 mN, with the optimal pre‐tension as determined earlier (Labruijere et al, ). Changes in tissue tension were measured with an isometric force transducer (Harvard, South Natick, MA, USA) and recorded on a flatbed recorder (Servogor 124, Goerz, Neudorf, Austria).…”

Section: Methodsmentioning

confidence: 99%

“…After further washout, a concentration–response curve to vehicle, sumatriptan, or lasmiditan was constructed, using whole logarithmic steps from 1 nM up to 10 μM. After finishing the curve and washing several times until reaching equilibrium, the functional integrity of the endothelium was verified by observing relaxation to substance P (10 nM; coronary and meningeal arteries) or bradykinin (1 μM; mammary arteries), after precontraction with the TxA 2 analogue U46619 (10–100 nM; Chan et al, ; Labruijere et al, ).…”

Section: Methodsmentioning

confidence: 99%

“…Currently, the specific therapies for acute antimigraine treatment are the triptans, selective 5‐HT 1B / 1D receptor agonists that also display varying levels of 5‐HT 1F receptor affinity. Unfortunately, not all patients respond to triptans (Diener & Limmroth, ), and they are contraindicated in patients with cardiovascular disease, due to their contractile properties via activation of 5‐HT 1B receptors in coronary arteries (Chan et al, ; Dodick et al, ; Labruijere et al, ; MaassenVanDenBrink, Reekers, Bax, Ferrari, & Saxena, ). Therefore, there is a need for novel antimigraine drugs for the patients that do not respond to the current available treatments, but also, for those patients with cardiovascular disease.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Characterization of binding, functional activity, and contractile responses of the selective 5‐HT_1F receptor agonist lasmiditan

Rubio‐Beltrán¹,

Labastida-Ramírez²,

Haanes³

et al. 2019

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

Background and Purpose:Triptans are 5-HT 1B/1D receptor agonists (that also display 5-HT 1F receptor affinity) with antimigraine action, contraindicated in patients with coronary artery disease due to their vasoconstrictor properties. Conversely, lasmiditan was developed as an antimigraine 5-HT 1F receptor agonist. To assess the selectivity and cardiovascular effects of lasmiditan, we investigated the binding, functional activity, and in vitro/in vivo vascular effects of lasmiditan and compared it to sumatriptan.Experimental Approach: Binding and second messenger activity assays of lasmiditan and other serotoninergic agonists were performed for human 5-HT 1A , 5-HT 1B , 5-HT 1D , 5-ht 1E , 5-HT 1F , 5-HT 2A , 5-HT 2B , and 5-HT 7 receptors, and the results were correlated with their potency to constrict isolated human coronary arteries (HCAs). Furthermore, concentration-response curves to lasmiditan and sumatriptan were performed in proximal and distal HCA, internal mammary, and middle meningeal arteries. Finally, anaesthetized female beagle dogs received i.v. infusions of lasmiditan or sumatriptan in escalating cumulative doses, and carotid and coronary artery diameters were measured.Key Results: Lasmiditan showed high selectivity for 5-HT 1F receptors. Moreover, the functional potency of the analysed compounds to inhibit cAMP increase through 5-HT 1B receptor activation positively correlated with their potency to contract HCA.In isolated human arteries, sumatriptan, but not lasmiditan, induced contractions.Likewise, in vivo, sumatriptan decreased coronary and carotid artery diameters at clinically relevant doses, while lasmiditan was devoid of vasoconstrictor activity at all doses tested. ---This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Conclusions and Implications:Lasmiditan is a selective 5-HT 1F receptor agonist devoid of vasoconstrictor activity. This may represent a cardiovascular safety advantage when compared to the triptans. SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Rubio-Beltrán E, Labastida-Ramírez A, Haanes KA, et al. Characterization of binding, functional activity, and contractile responses of the selective 5-HT 1F receptor agonist lasmiditan. Br J Pharmacol. 2019; https://doi.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of binding, functional activity, and contractile responses of the selective 5‐HT_1F receptor agonist lasmiditan

Rubio‐Beltrán¹,

Labastida-Ramírez²,

Haanes³

et al. 2019

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…vasodilatation) that has been advocated as a mechanism of headache and associated symptoms [6]. Interestingly, sumatriptan (a 5-HT 1B/1D receptor agonist with acute antimigraine properties) seems to exert part of its antinociceptive action by constricting the human middle meningeal artery (MMA) [7, 8]. In contrast, isometheptene racemate failed to constrict the porcine MMA [9], but the fact that it produces severe arterial vasospasm [10, 11] supports its vasoactive action on dilated cranial and cerebral arterioles [12, 13].…”

Section: Introductionmentioning

confidence: 99%

Pharmacological analysis of the increases in heart rate and diastolic blood pressure produced by (S)-isometheptene and (R)-isometheptene in pithed rats

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundIsometheptene is a sympathomimetic drug effective in acute migraine treatment. It is composed of two enantiomers with diverse pharmacological properties. This study investigated in pithed rats the cardiovascular effects of (S)- isometheptene and (R)-isometheptene, and the pharmacological profile of the more potent enantiomer.MethodsThe effects of i.v. bolus injections (0.03, 0.1, 0.3, 1 and 3 mg/kg) of isometheptene racemate, (S)-isometheptene or (R)-isometheptene on heart rate and blood pressure were analyzed in control experiments. The enantiomer producing more pronounced tachycardic and/or vasopressor responses was further analyzed in rats receiving i.v. injections of prazosin (0.1 mg/kg), rauwolscine (0.3 mg/kg), propranolol (1 mg/kg) or intraperitoneal reserpine (5 mg/kg, -24 h).ResultsCompared to (R)-isometheptene, (S)-isometheptene produced greater vasopressor responses, whilst both compounds equipotently increased heart rate. The tachycardic responses to (S)-isometheptene were abolished after propranolol, but remained unaffected by the other antagonists. In contrast, the vasopressor responses to (S)-isometheptene were practically abolished after prazosin. Interestingly, after reserpine, the tachycardic responses to (S)-isometheptene were abolished, whereas its vasopressor responses were attenuated and subsequently abolished by prazosin.ConclusionsThe different cardiovascular effects of the isometheptene enantiomers are probably due to differences in their mechanism of action, namely: (i) a mixed sympathomimetic action for (S)-isometheptene (a tyramine-like action and a direct stimulation of α1-adrenoceptors); and (ii) exclusively a tyramine like action for (R)-isometheptene. Thus, (R)-isometheptene may represent a superior therapeutic benefit as an antimigraine agent.

show abstract

“…DHE reduces carotid arteriovenous anastomosis via the 5HT1B receptor and α2A/2C adrenoreceptor agonism in a dose-dependent fashion [9]. DHE and its metabolites (8'-OH-DHE and 8',10'-OH DHE) also reduce venous compliance [6], and it is a more potent vasoconstrictor than meningeal/coronary arterial vasoconstrictor [10,11]. Here, we report a previously DHE-tolerant patient developing DHE-triggered vasospasm possibly facilitated by valproic acid and erenumab.…”

Section: Introductionmentioning

confidence: 82%

Acute Reversible Cerebral Vasoconstriction Syndrome With Low-Dose Dihydroergotamine Possibly Potentiated by Valproic Acid and Erenumab: A Case Report

Yuan¹,

Nahas²,

Berk³

2020

J Neurol Res

View full text Add to dashboard Cite

Dihydroergotamine (DHE), in the setting of polypharmacy, may increase the possibility of reversible cerebral vasoconstriction syndrome (RCVS). A 64-year-old woman with chronic migraine and medication-overuse headache (on amitriptyline, duloxetine, erenumab) was electively admitted for 5 days of intravenous (IV) ketamine (up to 55 mg/h) to treat intractable migraine pain. On the seventh day, upon receiving her forth dose of IV DHE (0.25 mg) and the first of IV valproic acid (VPA) (500 mg) adjunctively, she developed acute bilateral decreased visual acuity, bitemporal visual field deficit, and unsteady gait. Brain magnetic resonance imaging/magnetic resonance angiography (MRI/MRA) showed confluent bilateral T2 hyperintensities with punctate restricted diffusion in the occipital lobes associated with multi-segmental narrowing involving anterior, middle, posterior cerebral, and basilar arteries consistent with RCVS. Verapamil was initiated, whereas DHE, neuroleptics, and serotonergic agents were discontinued. Though she continued to have constant, non-thunderclap migrainous headache, her other neurologic symptoms resolved in 24 h. Concomitant use of VPA and erenumab with DHE may result in RCVS. VPA likely displaces the protein-bound DHE causing a transient surge of free DHE level in the serum. Erenumab may have impaired the protective vasodilatory mechanism, augmenting DHE's vasoconstrictive effect. This case report highlights the importance and awareness of such a drug-drug interaction with DHE.

show abstract

Dihydroergotamine and sumatriptan in isolated human coronary artery, middle meningeal artery and saphenous vein

Cited by 18 publications

References 32 publications

Characterization of binding, functional activity, and contractile responses of the selective 5‐HT_1F receptor agonist lasmiditan

Characterization of binding, functional activity, and contractile responses of the selective 5‐HT_1F receptor agonist lasmiditan

Pharmacological analysis of the increases in heart rate and diastolic blood pressure produced by (S)-isometheptene and (R)-isometheptene in pithed rats

Acute Reversible Cerebral Vasoconstriction Syndrome With Low-Dose Dihydroergotamine Possibly Potentiated by Valproic Acid and Erenumab: A Case Report

Contact Info

Product

Resources

About

Dihydroergotamine and sumatriptan in isolated human coronary artery, middle meningeal artery and saphenous vein

Cited by 18 publications

References 32 publications

Characterization of binding, functional activity, and contractile responses of the selective 5‐HT1F receptor agonist lasmiditan

Characterization of binding, functional activity, and contractile responses of the selective 5‐HT1F receptor agonist lasmiditan

Pharmacological analysis of the increases in heart rate and diastolic blood pressure produced by (S)-isometheptene and (R)-isometheptene in pithed rats

Acute Reversible Cerebral Vasoconstriction Syndrome With Low-Dose Dihydroergotamine Possibly Potentiated by Valproic Acid and Erenumab: A Case Report

Contact Info

Product

Resources

About

Characterization of binding, functional activity, and contractile responses of the selective 5‐HT_1F receptor agonist lasmiditan

Characterization of binding, functional activity, and contractile responses of the selective 5‐HT_1F receptor agonist lasmiditan