Progress in the Discovery of Ca Channel Blockers for the Treatment of Pain

Beswick, Paul J.

doi:10.1016/b978-0-12-409547-2.12438-2

Cited by 4 publications

(7 citation statements)

References 166 publications

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“…Both ω-agatoxins bind on the outside of the pore region of α1a subunit of CaV2.1 but have different kinetics: blocking by ω-agatoxin IVB is eightfold slower than IVA [ 127 ]. However, there are drugs that are not selective for but act also at CaV2.1 and show clinical efficacy in patients with FHM1 including flunarizine and the non-dihydropyridine verapamil [ 128 ].…”

Section: Structure and Functions Of Cav21mentioning

confidence: 99%

Migraine: Calcium Channels and Glia

Kowalska

Prendecki

Piekut

et al. 2021

IJMS

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Migraine is a common neurological disease that affects about 11% of the adult population. The disease is divided into two main clinical subtypes: migraine with aura and migraine without aura. According to the neurovascular theory of migraine, the activation of the trigeminovascular system (TGVS) and the release of numerous neuropeptides, including calcitonin gene-related peptide (CGRP) are involved in headache pathogenesis. TGVS can be activated by cortical spreading depression (CSD), a phenomenon responsible for the aura. The mechanism of CSD, stemming in part from aberrant interactions between neurons and glia have been studied in models of familial hemiplegic migraine (FHM), a rare monogenic form of migraine with aura. The present review focuses on those interactions, especially as seen in FHM type 1, a variant of the disease caused by a mutation in CACNA1A, which encodes the α1A subunit of the P/Q-type voltage-gated calcium channel.

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Section: Structure and Functions Of Cav21mentioning

confidence: 99%

Migraine: Calcium Channels and Glia

Kowalska

Prendecki

Piekut

et al. 2021

IJMS

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“…1 ), a state-dependent Ca V 2.2 inhibitor originally developed by Zalicus Pharmaceuticals, a subsidiary of Epirus Pharmaceuticals, was well tolerated in Phase I clinical trials, however, Z160 4 failed to demonstrate efficacy in patients with lumbosacral radiculopathy and post-herpetic neuralgia during the relevant phase II clinical evaluations. 34 Similarly, the drug ABT-639 5 ( Fig. 1 ), a potent Ca V 3.2 blocker developed by AbbVie, failed to demonstrate analgesic efficacy in patients with diabetic neuropathy and was eventually terminated during phase II clinical trials.…”

Section: Introductionmentioning

confidence: 99%

“…1), a potent Ca V 3.2 blocker developed by AbbVie, failed to demonstrate analgesic efficacy in patients with diabetic neuropathy and was eventually terminated during phase II clinical trials. [34][35][36][37] Due to the limited availability of effective medications for the management of neuropathic pain, our research investigations have focused on the discovery of small molecule Ca V 2.2 and Ca V 3.2 inhibitors with a number of phenoxyanilides being evaluated for their activity at the two calcium ion channels (representative structures are shown in Fig. 2).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of N-type calcium channels by phenoxyaniline and sulfonamide analogues

Bispat,

Cardoso,

Hasan

et al. 2024

RSC Med. Chem.

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“…The N-type calcium ion channel is an established target for the treatment of neuropathic pain. 18 The channel consists of a unique α1 pore-forming subunit and auxiliary α2-δ and β subunits. The general structure of the α1 subunit is similar to that of other voltage-gated ion channels, comprising a single protein chain arranging itself into four domains (I-IV), each consisting of six transmembrane segments S1-S6 (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…Fig 18. Image showing the structures resulting from the MD simulation run on the Ca V 2.2trimipramine docked complex.…”

mentioning

confidence: 99%