User:Fvasconcellos/Retigabine
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| Routes of administration | Oral |
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| Pharmacokinetic data | |
| Bioavailability | 60% |
| Protein binding | 60–80% |
| Metabolism | Hepatic glucuronidation and acetylation. CYP not involved |
| Elimination half-life | 8 hours (mean)[1] |
| Excretion | Renal (84%) |
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Retigabine (
Retigabine works primarily as a potassium channel opener—that is, by activating a certain family of voltage-gated potassium channels in the brain.[3][4][5] This mechanism of action is unique among antiepileptic drugs, and may hold promise for the treatment of other neurologic conditions, including migraine and neuropathic pain; a Phase II trial to assess the safety and efficacy of retigabine for treating postherpetic neuralgia is ongoing.
History
Among the newer anticonvulsants, retigabine was one of the most widely studied in the
Preclinical testing
Several animal studies have suggested that, like many antiepileptic drugs, retigabine may act as a mood stabilizer.[8][9][10]
Clinical trials
In a
Adverse effects
The adverse effects found in the Phase II trial mainly affected the central nervous system, and appeared to be dose-related.[7] The most common adverse effects were drowsiness, dizziness and vertigo, confusion, and slurred speech.[12] Less common side effects included tremor, memory loss, gait disturbances, and double vision.[11]
Pharmacokinetics
Retigabine is quickly absorbed, and reaches maximum plasma concentrations in 1.5 hours after a single oral dose. It has a moderately high oral bioavailability (50–60%), a high volume of distribution (6.2 L/kg), and a terminal half-life of 8 to 11 hours.[13] Retigabine appears to require thrice-daily dosing due to its short half-life.[12][7]
Retigabine is metabolized in the liver, by N-glucuronidation and acetylation. The cytochrome P450 system is not involved. Retigabine and its metabolites are excreted by the kidneys.[13]
Mechanism of action
Retigabine acts as a neuronal KCNQ/Kv7 potassium channel opener, a mechanism of action markedly different from than of any current anticonvulsants.[3][4][14] This mechanism of action is similar to that of flupirtine,[15] which is used mainly for its analgesic properties.
Interactions
Retigabine appears to be free of
References
- S2CID 5568963.)
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- ^ PMID 10908292.)
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- ^ PMID 18049722.
- S2CID 45545956.)
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- ^ S2CID 24574886.)
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link - ^ PMID 16800718.
- ^ PMID 19443931.
- PMID 18590620.
- PMID 19298256.
Further reading
- Blackburn-Munro G, Dalby-Brown W, Mirza NR, Mikkelsen JD, Blackburn-Munro RE (2005). "Retigabine: chemical synthesis to clinical application". CNS Drug Rev. 11 (1): 1–20. PMID 15867950.)
{{cite journal}}: CS1 maint: multiple names: authors list (link - Hempel R, Schupke H, McNeilly PJ; et al. (1999). "Metabolism of retigabine (D-23129), a novel anticonvulsant". Drug Metab Dispos. 27 (5): 613–22. PMID 10220491.)
{{cite journal}}: Explicit use of et al. in:|author=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link