Design, synthesis, and structure – Activity relationship studies of novel tryptamine derivatives as 5‑HT1B receptor agonists

Fang, Liping; He, Shan; Yin, Peng; Wang, Ning; Zhang, Bin; Jin, Haixiao

doi:10.1016/j.molstruc.2022.133320

Cited by 6 publications

(5 citation statements)

References 41 publications

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“…The mechanism of action of triptans is based on increasing the serotonin signal by stimulating the serotonin receptors in the cranial blood vessels and nerve endings and inhibiting the release of peptides such as CGRP and substance P. Triptans provide high treatment success by selectively binding to 5-HT1B/1D receptors. It is thought that they may have cardiovascular side effects due to their vasoconstrictor effects on smooth muscles. , Structure–activity studies on triptan and its derivatives have shown that substituents at the 5-position increase the agonist activity of the 5-HT1B receptor, and the tryptamine moiety provides hydrophobic, ionic, and hydrogen bond interactions …”

Section: Migraine Drugs and Their Synthesismentioning

confidence: 99%

Migraine and Its Treatment from the Medicinal Chemistry Perspective

Pehlivanlar,

Carradori,

Simsek

2024

ACS Pharmacol. Transl. Sci.

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Migraine is a disease of neurovascular origin that affects the quality of life of more than one billion people and ranks sixth among the most common diseases in the world. Migraine is characterized by a moderate or severe recurrent and throbbing headache, accompanied by nausea, vomiting, and photo-phonophobia. It usually starts in adolescence and is twice as common in women as in men. It is classified as with or without aura and has chronic or acute treatment types according to the frequency of occurrence. In acute treatment, analgesics that relieve pain in the fastest way are preferred, while there are different options in chronic treatment. While non-specific methods were used in the treatment of migraine until the 1950s, triptans, ditans, and CGRP-receptor-dependent therapies (monoclonal antibodies and gepants) started to be used in the clinic more recently. In this Review, we focus on the synthesis, side effects, and pharmacological and pharmacokinetic properties of FDA-approved drugs used in acute and preventive-specific treatment of migraine.

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Section: Migraine Drugs and Their Synthesismentioning

confidence: 99%

Migraine and Its Treatment from the Medicinal Chemistry Perspective

Pehlivanlar,

Carradori,

Simsek

2024

ACS Pharmacol. Transl. Sci.

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“…When triptan drugs act as 5-HT receptor agonists and bind to 5-HT 1B/1D receptors coupled with Gi proteins, they cause a decrease of cAMP levels in cells, resulting in a reduction of CGRP released from trigeminal nerve cells, ultimately reducing nociceptive transmission. [10][11][12] 5-HT receptor agonists mainly relieve migraine attacks by activating 5-HT 1A/B/D receptors, causing vasoconstriction and lowering cAMP levels when acting on 5-HT 1B receptors, inhibiting CGRP release from C-fibers through voltage-gated calcium channels. 13,14 Triptan-based drugs act as 5-HT 1B/1D receptor agonists and have been used as the first choice specific drugs for acute treatment of migraine, 15 and it significantly inhibit CGRP release from trigeminal nerve terminals by binding and activating presynaptic 5-HT 1D and 5-HT 1F receptors.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rizatriptan benzoate-loaded dissolving microneedle patch for management of acute migraine therapy

Zhong,

Zhang,

Sun

et al. 2024

J Biomater Appl

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In this study, dissolving microneedles (MNs) using polyvinyl alcohol (PVA) and poly (1-vinylpyrrolidone-co-vinyl acetate) (P(VP-co-VA)) as matrix materials were developed for transdermal delivery of rizatriptan benzoate (RB) for acute migraine treatment. In-vitro permeation studies were conducted to assess the feasibility of the as-fabricated dissolving MNs to release RB. Drug skin penetration were tested by Franz diffusion cells, showing an increase of the transdermal flux compared to passive diffusion due to the as-fabricated dissolving MNs having a sufficient mechanical strength to penetrate the skin and form microchannels. The pharmacological study in vivo showed that RB-loaded dissolving MNs significantly alleviated migraine-related response by up-regulating the level of 5-hydroxytryptamine (5-HT) and down-regulating the levels of calcitonin gene-related peptide (CGRP) and substance P (SP). In conclusion, the RB-loaded dissolving MNs have advantages of safety, convenience, and high efficacy over conventional administrations, laying a foundation for the transdermal drug delivery system treatment for acute migraine.

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“…When triptan drugs act as 5-HT receptor agonists and bind to 5-HT 1B/1D receptors coupled with Gi proteins, they cause a decrease in cAMP levels in cells, resulting in a reduction of CGRP released from trigeminal nerve cells, ultimately reducing nociceptive transmission. [10][11][12] 5-HT can counteract CGRP-mediated migraine processes as a serotonergic drug. [13] 5-HT drugs mainly relieve migraine attacks by agonizing 5-HT 1A/B/D receptors, causing vasoconstriction and lowering cAMP levels when acting on 5-HT 1B receptors, inhibiting CGRP release from C-bers through voltage-gated calcium channels.…”

Section: Introductionmentioning

confidence: 99%

Rizatriptan benzoate-loaded dissolving microneedle patch for management of acute migraine

Zhong,

Zhang,

Shen

et al. 2023

Preprint

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In this study, dissolving microneedles (MNs) using polyvinyl alcohol (PVA) and poly(1-vinylpyrrolidone-co-vinyl acetate) copolymers (PVP-VA) as the matrix has been developed for transdermal delivery of rizatriptan benzoate (RB) for acute migraine treatment. In-vitro permeation studies were conducted to assess the feasibility of fabricating dissolving MNs to release RB. Franz diffusion cell tests showed higher transdermal flux with dissolving MNs compared to passive diffusion. This was due to the MNs' mechanical strength, enabling them to penetrate the skin and form microchannels.The in vivo pharmacological study demonstrated that dissolving microneedles (MNs) loaded with RB effectively reduced migraine-related symptoms. This was achieved by increasing the level of 5-hydroxytryptamine (5-HT) and decreasing the levels of calcitonin gene-related peptide (CGRP) and substance P (SP).In conclusion, the RB-loaded dissolving MNs offer several advantages compared to conventional administrations methods, including safety, convenience, and high efficacy. These findings provide a promising basis for the development of transdermal drug delivery systems for the treatment of acute

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Design, synthesis, and structure – Activity relationship studies of novel tryptamine derivatives as 5‑HT1B receptor agonists

Cited by 6 publications

References 41 publications

Migraine and Its Treatment from the Medicinal Chemistry Perspective

Migraine and Its Treatment from the Medicinal Chemistry Perspective

Rizatriptan benzoate-loaded dissolving microneedle patch for management of acute migraine therapy

Rizatriptan benzoate-loaded dissolving microneedle patch for management of acute migraine

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