Pharmacology and mechanism of action of pregabalin: The calcium channel α2–δ (alpha2–delta) subunit as a target for antiepileptic drug discovery

@article{Taylor2007PharmacologyAM,
  title={Pharmacology and mechanism of action of pregabalin: The calcium channel $\alpha$2–$\delta$ (alpha2–delta) subunit as a target for antiepileptic drug discovery},
  author={Charles Price Taylor and Timothy P. Angelotti and Eric B Fauman},
  journal={Epilepsy Research},
  year={2007},
  volume={73},
  pages={137-150}
}
Summary Pregabalin (Lyrica™) is a new antiepileptic drug that is active in animal seizure models. Pregabalin is approved in US and Europe for adjunctive therapy of partial seizures in adults, and also has been approved for the treatment of pain from diabetic neuropathy or post-herpetic neuralgia in adults. Recently, it has been approved for treatment of anxiety disorders in Europe. Pregabalin is structurally related to the antiepileptic drug gabapentin and the site of action of both drugs is… Expand
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This review proposes how binding to the α2-δ protein target in different regions of the CNS may contribute to the observed clinical activity of pregabalin, as well as to the adverse event profile of the compound. Expand
Pregabalin is a potent and selective ligand for α(2)δ-1 and α(2)δ-2 calcium channel subunits.
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Pregabalin did not interact with any of the 38 receptors and ion channels evaluated, and a variety of central nervous system (CNS)-targeted therapeutic drugs did not show activity at the α(2)δ subunits of voltage-gated calcium channels. Expand
Mechanisms of analgesia by gabapentin and pregabalin – Calcium channel α2-δ [Cavα2-δ] ligands
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It is concluded that gabapentin and pregabalin are not GABAergic and instead reduce the stimulated release of transmitters by binding at calcium channel alpha-delta (CaVa2-d) proteins. Expand
Analgesia with Gabapentin and Pregabalin May Involve N-Methyl-d-Aspartate Receptors, Neurexins, and Thrombospondins
  • C. Taylor, E. Harris
  • Medicine, Chemistry
  • The Journal of Pharmacology and Experimental Therapeutics
  • 2020
TLDR
Findings show that the α2δ-1 protein also interacts with N-methyl-d-aspartate–sensitive glutamate receptors, neurexin-1α, thrombospondins (adhesion molecules), and other presynaptic proteins, and these newly discovered interactions, in addition to actions at calcium channels, may be important mediators of gabapentin and pregabalin therapeutic effects. Expand
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The rapid onset of action with significant antiepileptic effects at dosages of 150 – 600 mg/day makes pregabalin an option in patients with high seizure frequency and favorable effects on mood offer advantages in many patients with chronic epilepsy and psychiatric comorbidities. Expand
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Gabapentin and pregabalin are effective for the treatment neuropathic pain, fibromyalgia and epilepsy; in addition, they may be useful for the reduction of postoperative pain. Expand
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Pregabalin was found effective as adjunctive therapy for refractory partial-onset seizures, with up to 51% responder at a dose of 600 mg/day, and the lowest effective dose was 150mg/day. Expand
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Evidence indicates that GBP may act chronically by displacing an endogenous ligand that is normally a positive modulator of α2δ subunit function, thereby impairing the trafficking function of the α2 δ subunits to which it binds. Expand
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Abstract Pregabalin, (( S )-3-(aminomethyl)-5-methylhexanoic acid, also known as ( S )-3-isobutyl GABA, Lyrica™) is approved for treatment of certain types of peripheral neuropathic pain and as anExpand
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