ガバペンチン
WordNet
- an anticonvulsant (trade name Neurontin) used to control some types of seizures in the treatment of epilepsy; also used to manage neuralgia caused by shingles (同)Neurontin
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/12/15 11:28:36」(JST)
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Gabapentin enacarbil
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| Clinical data |
| Trade names |
Horizant, Regnite |
| License data |
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Pregnancy
category |
- US: C (Risk not ruled out)
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Routes of
administration |
Oral |
| Legal status |
| Legal status |
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| Pharmacokinetic data |
| Excretion |
Renal |
| Identifiers |
IUPAC name
- (1-{[({(1RS)-1-[isobutyryloxy]ethoxy}carbonyl)
amino]methyl}cyclohexyl)acetic acid
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| CAS Number |
478296-72-9 Y |
| PubChem (CID) |
9883933 |
| IUPHAR/BPS |
7560 |
| ChemSpider |
8059607 N |
| UNII |
75OCL1SPBQ N |
| ChEBI |
CHEBI:68840 N |
| Chemical and physical data |
| Formula |
C16H27NO6 |
| Molar mass |
329.389 g/mol |
| 3D model (Jmol) |
Interactive image |
SMILES
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CC(C)C(=O)OC(C)OC(=O)NCC1(CCCCC1)CC(=O)O
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InChI
-
InChI=1S/C16H27NO6/c1-11(2)14(20)22-12(3)23-15(21)17-10-16(9-13(18)19)7-5-4-6-8-16/h11-12H,4-10H2,1-3H3,(H,17,21)(H,18,19) N
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Key:TZDUHAJSIBHXDL-UHFFFAOYSA-N N
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| NY (what is this?) (verify) |
Gabapentin enacarbil (Horizant (in USA), Regnite (in Japan), formerly known as XP-13512) is a prodrug for the anticonvulsant and analgesic drug gabapentin.[1] It was designed for increased oral bioavailability over gabapentin,[2][3] and human trials showed it to produce extended release of gabapentin with almost twice the overall bioavailability,[4] especially when taken with a fatty meal.[5] Gabapentin enacarbil has passed human clinical trials for the treatment of restless legs syndrome, and initial results have shown it to be well tolerated and reasonably effective.[6][7][8]
Gabapentin enacarbil was denied approval by the U.S. Food and Drug Administration (FDA) in February 2010, citing concerns about possible increased cancer risk shown by some animal studies. Similar concerns had been raised about gabapentin itself in the past, but were felt to be outweighed by its clinical utility as an anticonvulsant, whereas the treatment of restless legs syndrome was not seen to justify the same kind of risk.[9]
On April 6, 2011, Xenoport received FDA approval for Horizant (gabapentin enacarbil) for the treatment of moderate-to-severe restless legs syndrome.[10] On June 7, 2012, FDA approved Horizant for the treatment of postherpetic neuralgia in adults.[11]
See also
- Atagabalin
- 4-Methylpregabalin
References
- ^ Landmark CJ, Johannessen SI (2008). "Modifications of antiepileptic drugs for improved tolerability and efficacy". Perspectives in Medicinal Chemistry. 2: 21–39. PMC 2746576. PMID 19787095.
- ^ Cundy KC, Branch R, Chernov-Rogan T, Dias T, Estrada T, Hold K, Koller K, Liu X, Mann A, Panuwat M, Raillard SP, Upadhyay S, Wu QQ, Xiang JN, Yan H, Zerangue N, Zhou CX, Barrett RW, Gallop MA (October 2004). "XP13512 [(+/-)-1-([(alpha-isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane acetic acid], a novel gabapentin prodrug: I. Design, synthesis, enzymatic conversion to gabapentin, and transport by intestinal solute transporters". The Journal of Pharmacology and Experimental Therapeutics. 311 (1): 315–23. doi:10.1124/jpet.104.067934. PMID 15146028.
- ^ Cundy KC, Annamalai T, Bu L, De Vera J, Estrela J, Luo W, Shirsat P, Torneros A, Yao F, Zou J, Barrett RW, Gallop MA (October 2004). "XP13512 [(+/-)-1-([(alpha-isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane acetic acid], a novel gabapentin prodrug: II. Improved oral bioavailability, dose proportionality, and colonic absorption compared with gabapentin in rats and monkeys". The Journal of Pharmacology and Experimental Therapeutics. 311 (1): 324–33. doi:10.1124/jpet.104.067959. PMID 15146029.
- ^ Cundy KC, Sastry S, Luo W, Zou J, Moors TL, Canafax DM (December 2008). "Clinical pharmacokinetics of XP13512, a novel transported prodrug of gabapentin". Journal of Clinical Pharmacology. 48 (12): 1378–88. doi:10.1177/0091270008322909. PMID 18827074.
- ^ Lal R, Sukbuntherng J, Luo W, Huff FJ, Zou J, Cundy KC (February 2010). "The effect of food with varying fat content on the clinical pharmacokinetics of gabapentin after oral administration of gabapentin enacarbil". International Journal of Clinical Pharmacology and Therapeutics. 48 (2): 120–8. doi:10.5414/cpp48120. PMID 20137764.
- ^ Merlino G, Serafini A, Lorenzut S, Sommaro M, Gigli GL, Valente M (January 2010). "Gabapentin enacarbil in restless legs syndrome". Drugs of Today (Barcelona, Spain : 1998). 46 (1): 3–11. doi:10.1358/dot.2010.46.1.1424766. PMID 20200691.
- ^ Bogan RK, Bornemann MA, Kushida CA, Trân PV, Barrett RW (June 2010). "Long-term maintenance treatment of restless legs syndrome with gabapentin enacarbil: a randomized controlled study". Mayo Clinic Proceedings. Mayo Clinic. 85 (6): 512–21. doi:10.4065/mcp.2009.0700. PMC 2878254. PMID 20511481.
- ^ Imamura S, Kushida C (August 2010). "Gabapentin enacarbil (XP13512/GSK1838262) as an alternative treatment to dopaminergic agents for restless legs syndrome". Expert Opinion on Pharmacotherapy. 11 (11): 1925–32. doi:10.1517/14656566.2010.494598. PMID 20629607.
- ^ GlaxoSmithKline/XenoPort: FDA setback halts gabapentin reformulations
- ^ [1][dead link]
- ^ Jeffrey, Susan. "FDA Approves Gabapentin Enacarbil for Postherpetic Neuralgia". Medscape.
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Anticonvulsants (N03)
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| GABAergics |
| GABAAR PAMs |
- Barbiturates: Barbexaclone
- Metharbital
- Methylphenobarbital
- Pentobarbital
- Phenobarbital#
- Primidone; Carbamates: Felbamate; Benzodiazepines: Clobazam
- Clonazepam
- Clorazepate
- Diazepam#
- Lorazepam#
- Midazolam
- Nimetazepam
- Nitrazepam
- Temazepam; Others: Bromide (potassium bromide, sodium bromide)
- Paraldehyde
- Stiripentol
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|
| GABA-T inhibitors |
- Fatty acids: Valproate
- Valpromide
- Valproate pivoxil; Others: Ethanolamine-O-sulfate
- Vigabatrin
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|
| Others |
- GABAR agonists: Progabide; GAT-1 inhibitors: Tiagabine
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|
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| Channelergics |
| Sodium blockers |
- Hydantoins: Ethotoin
- Fosphenytoin
- Mephenytoin
- Phenytoin#; Ureides: Acetylpheneturide
- Chlorphenacemide
- Phenacemide‡
- Pheneturide; Fatty acids: Valproate
- Valpromide
- Valproate pivoxil; Carboxamides: Carbamazepine#
- Eslicarbazepine acetate
- Oxcarbazepine; Others: Lacosamide
- Lamotrigine
- Rufinamide
- Topiramate
- Zonisamide
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|
| Calcium blockers |
- Oxazolidinediones: Ethadione
- Paramethadione
- Trimethadione; Succinimides: Ethosuximide#
- Mesuximide
- Phensuximide; Gabapentinoids: Gabapentin
- Pregabalin; Others: Lamotrigine
- Topiramate
- Zonisamide
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| Potassium openers |
|
|
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| Others |
| CA inhibitors |
- Sulfonamides: Acetazolamide
- Ethoxzolamide
- Sultiame
- Topiramate
- Zonisamide
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|
| Others |
- Beclamide
- Brivaracetam
- Levetiracetam
- Perampanel
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|
|
- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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Neuropathic pain and fibromyalgia pharmacotherapies
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| Monoaminergics |
- SNRIs (e.g., duloxetine, milnacipran)
- TCAs (e.g., amitriptyline, nortriptyline, dosulepin)
- Tapentadol
- Tramadol
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|
| Ion channel blockers |
- Anticonvulsants (e.g., gabapentin, pregabalin, carbamazepine, oxcarbazepine, lacosamide, lamotrigine)
- Local anesthetics (e.g., lidocaine)
- Mexiletine
- TCAs (e.g., amitriptyline, nortriptyline, desipramine)
- Ziconotide
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| Others |
- Alpha lipoic acid
- Benfotiamine
- Botulinum toxin A
- Bupropion
- Cannabinoids (e.g., cannabis, dronabinol, nabilone)
- NMDAR antagonists (e.g., ketamine, dextromethorphan, methadone)
- Opioids (e.g., hydrocodone, morphine, oxycodone, methadone, buprenorphine, tramadol, tapentadol)
- Sodium oxybate (GHB)
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Anxiolytics (N05B)
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| 5-HT1A agonists |
|
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| GABAAR PAMs |
- Benzodiazepines:
- Adinazolam
- Alprazolam
- Bromazepam
- Camazepam
- Chlordiazepoxide
- Clobazam
- Clonazepam
- Clorazepate
- Clotiazepam
- Cloxazolam
- Diazepam#
- Ethyl loflazepate
- Etizolam
- Fludiazepam
- Halazepam
- Ketazolam
- Lorazepam#
- Medazepam
- Nordazepam
- Oxazepam
- Pinazepam
- Prazepam
- Others: Alpidem‡
- Barbiturates
- Carbamates
- Chlormezanone‡
- Ethanol
- Etifoxine; Herbs:
- Kava
- Skullcap
- Valerian
|
|
| α2δ VDCC blockers |
- Gabapentin
- Gabapentin enacarbil
- Phenibut
- Pregabalin
|
|
| Antidepressants |
- SSRIs
- SNRIs
- SARIs
- TCAs
- TeCAs
- MAOIs; Others: Agomelatine
- Bupropion
- Vilazodone
- Vortioxetine
|
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| Sympatholytics |
- Beta blockers (e.g., propranolol)
- Clonidine
- Dexmedetomidine
- Guanfacine
- Prazosin
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| Others |
- Benzoctamine
- Cannabidiol
- Cycloserine
- Fabomotizole
- Hydroxyzine
- Kanna
- Lavender
- Lorpiprazole
- Mebicar
- Mepiprazole
- Nicotine
- Opipramol
- Oxaflozane‡
- Phenaglycodol
- Phenibut
- Picamilon
- Selank
- Tiagabine
- Tofisopam
- Validolum
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UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
English Journal
- Treatment response to sleep, pain, and mood disturbance and their correlation with sleep disturbance in adult patients with moderate-to-severe primary restless legs syndrome: Pooled analyses from 3 trials of gabapentin enacarbil.
- Bogan RK1, Lee DO, Buchfuhrer MJ, Jaros MJ, Kim R, Shang G.
- Annals of medicine.Ann Med.2015 Apr 15:1-9. [Epub ahead of print]
- INTRODUCTION: This pooled analysis investigated the effects of gabapentin enacarbil (GEn) on clinical correlates of sleep disturbance in adults with moderate-to-severe primary restless legs syndrome (RLS) and no-to-moderate or severe-to-very severe baseline sleep disturbance.METHODS: Co-primary en
- PMID 25874578
- Gabapentin enacarbil and morphine administered in combination versus alone: a double-blind, randomized, pharmacokinetic, and tolerability comparison.
- Chen C1, Upward J2, Arumugham T3, Stier B3, Davy M2.
- Clinical therapeutics.Clin Ther.2015 Feb 1;37(2):349-57. doi: 10.1016/j.clinthera.2014.10.015. Epub 2014 Nov 20.
- PURPOSE: Coadministration of morphine with oral gabapentin has been shown to increase plasma gabapentin concentrations. This study evaluated whether there was any interaction between gabapentin enacarbil (GEn), which is a prodrug of gabapentin, and morphine in terms of pharmacokinetics, pharmacodyna
- PMID 25467190
- A mixed treatment comparison of gabapentin enacarbil, pramipexole, ropinirole and rotigotine in moderate-to-severe restless legs syndrome.
- Sun Y1, van Valkenhoef G, Morel T.
- Current medical research and opinion.Curr Med Res Opin.2014 Nov;30(11):2267-78. doi: 10.1185/03007995.2014.946124. Epub 2014 Jul 31.
- OBJECTIVE: A mixed treatment comparison (MTC) was performed to investigate the relative efficacy and safety of licensed pharmaceuticals for moderate-to-severe restless legs syndrome (RLS).METHODS: RLS trials published over the past 10 years were identified via systematic literature searches of MEDLI
- PMID 25050588
Japanese Journal
- レストレスレッグス症候群の治療 (特集 ガバペンチン エナカルビルの基礎と臨床)
- ガバペンチン エナカルビルの基礎 (特集 ガバペンチン エナカルビルの基礎と臨床)
- 新規レストレスレッグス症候群治療薬カバペンチン エナカルビル(レグナイト^【○!R】錠)の薬理学的特徴および臨床試験成績
- 柿元 周一郎,小澤 徹,五十嵐 澄,得能 朝成,加来 聖司,関 信男
- 日本薬理學雜誌 = Folia pharmacologica Japonica 140(2), 85-92, 2012-08-01
- NAID 10030987220
Related Links
- Easy to read patient leaflet for gabapentin enacarbil Tablets. Includes indications, proper use, special instructions, precautions, and possible side effects. ... Disclaimer: This information should not be used to decide whether or not to ...
- Find patient medical information for gabapentin enacarbil oral on WebMD including its uses, side effects and safety, interactions, pictures, warnings and user ratings. ... This medication is used to treat moderate to ...
★リンクテーブル★
[★]
- 英
- gabapentin
- 化
- ガバペンチンエナカルビル gabapentin enacarbil
- 商
- (ガバペンチン)ガバペン、(ガバペンチンエナカルビル)レグナイト、Neurontin
- 同
- ギャバペンチン
- 関
- 抗てんかん薬
- その他の中枢神経系用薬
作用機序
- 1. 興奮性神経系の前シナプスにおいて電位依存性Caチャネルのα2δサブユニットへの結合を介してCaの流入を抑制することによりグルタミン酸などの神経伝達物質の遊離を抑制
- 2. 脳内GABA量を増加させ、GABAトランスポーターを活性化することによって抑制性神経系であるGABA神経系機能を維持・増強