Peringatan Keamanan

Oral TDLO reported in man is 3.14 mg/kg/42D (intermittent) MSDS. While limited cases of soft stool, belching, and abdominal bloating have been reported from dietary supplements containing gamolenic acid, daily doses up to 2.8 g were well tolerated F27.

Gamolenic acid

DB13854

small molecule approved investigational

Deskripsi

Gamolenic acid, or gamma-linolenic acid (?-Linolenic acid) or GLA, is an essential fatty acid (EFA) comprised of 18 carbon atoms with three double bonds F27 that is most commonly found in human milk and other botanical sources A32848. It is an omega-6 polyunsaturated fatty acid (PUFA) also referred to as 18:3n-6; 6,9,12-octadecatrienoic acid; and cis-6, cis-9, cis-12- octadecatrienoic acid F27. Gamolenic acid is produced minimally in the body as the delta 6-desaturase metabolite of DB00132. It is converted to DB00154, a biosynthetic precursor of monoenoic prostaglandins such as PGE1. While Gamolenic acid is found naturally in the fatty acid fractions of some plant seed oils F27, DB11358 and DB11238 are rich sources of gamolenic acid. Evening primrose oil has been investigated for clinical use in menopausal syndrome, diabetic neuropathy, and breast pain, where gamolenic acid is present at concentrations of 7-14% F27. Gamolenic acid may be found in over-the-counter dietary supplements. Gamolenic acid is also found in some fungal sources and also present naturally in the form of triglycerides F27. Various clinical indications of gamolenic acid have been studied, including rheumatoid arthritis, atopic eczema, acute respiratory distress syndrome, asthma, premenstrual syndrome, cardiovascular disease, ulcerative colitis, ADHD, cancer, osteoporosis, diabetic neuropathy, and insomnia.

Struktur Molekul 2D

Berat 278.4296
Wujud liquid

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) No pharmacokinetic data available.
Volume Distribusi No pharmacokinetic data available.
Klirens (Clearance) No pharmacokinetic data available.

Absorpsi

The findings from a pharmacokinetic study suggest that therapeutic levels of GLA can be achieved within a week. The fasting plasma GLA levels plateaued within seven days of beginning treatment, regardless of dose F27.

Metabolisme

Via elongation mediated by elongase (ELOVL5), gamolenic acid is rapidly converted to dihomo-gamma-linolenic acid (DGLA), which is further cyclooxygenated to prostaglandin E1 (PGE1) via COX-1 or COX-2 enzymatic activity depending on the cell type A32848. PGE1 may be metabolized to smaller prostaglandin remnants, primarily dicarboxylic acids, which undergo renal excretion F27. DGLA may be converted to 15-(S)-hydroxy-8,11,13-eicosatrienoic acid (15-HETrE) by 15-lipoxygenase enzyme A32848. Although the enzymatic pathway is less predominant relative to ELOVL5 in most cells, DGLA may also be converted to arachidonic acid (AA) via delta-5-desaturate activity A32852, where hydrogen atoms are selectively removed to create new double bonds F27]. Arachidonic acid is a precursor in the biosynthesis of prostaglandin E2, thromboxanes, and leukotrienes, which are potent inflammatory mediators and play an important role in inflammatory pathways.

Rute Eliminasi

The metabolites of gamolenic acid is expected to undergo renal excretion F27.

Interaksi Obat

91 Data
Lorazepam The therapeutic efficacy of Lorazepam can be decreased when used in combination with Gamolenic acid.
Pregabalin The therapeutic efficacy of Pregabalin can be decreased when used in combination with Gamolenic acid.
Butalbital The therapeutic efficacy of Butalbital can be decreased when used in combination with Gamolenic acid.
Phenytoin The therapeutic efficacy of Phenytoin can be decreased when used in combination with Gamolenic acid.
Topiramate The therapeutic efficacy of Topiramate can be decreased when used in combination with Gamolenic acid.
Pentobarbital The therapeutic efficacy of Pentobarbital can be decreased when used in combination with Gamolenic acid.
Valproic acid The therapeutic efficacy of Valproic acid can be decreased when used in combination with Gamolenic acid.
Trimethadione The therapeutic efficacy of Trimethadione can be decreased when used in combination with Gamolenic acid.
Clobazam The therapeutic efficacy of Clobazam can be decreased when used in combination with Gamolenic acid.
Secobarbital The therapeutic efficacy of Secobarbital can be decreased when used in combination with Gamolenic acid.
Metharbital The therapeutic efficacy of Metharbital can be decreased when used in combination with Gamolenic acid.
Methohexital The therapeutic efficacy of Methohexital can be decreased when used in combination with Gamolenic acid.
Mephenytoin The therapeutic efficacy of Mephenytoin can be decreased when used in combination with Gamolenic acid.
Lamotrigine The therapeutic efficacy of Lamotrigine can be decreased when used in combination with Gamolenic acid.
Carbamazepine The therapeutic efficacy of Carbamazepine can be decreased when used in combination with Gamolenic acid.
Ethosuximide The therapeutic efficacy of Ethosuximide can be decreased when used in combination with Gamolenic acid.
Thiopental The therapeutic efficacy of Thiopental can be decreased when used in combination with Gamolenic acid.
Paramethadione The therapeutic efficacy of Paramethadione can be decreased when used in combination with Gamolenic acid.
Clorazepic acid The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Gamolenic acid.
Magnesium sulfate The therapeutic efficacy of Magnesium sulfate can be decreased when used in combination with Gamolenic acid.
Tizanidine The therapeutic efficacy of Tizanidine can be decreased when used in combination with Gamolenic acid.
Riluzole The therapeutic efficacy of Riluzole can be decreased when used in combination with Gamolenic acid.
Ethotoin The therapeutic efficacy of Ethotoin can be decreased when used in combination with Gamolenic acid.
Oxcarbazepine The therapeutic efficacy of Oxcarbazepine can be decreased when used in combination with Gamolenic acid.
Primidone The therapeutic efficacy of Primidone can be decreased when used in combination with Gamolenic acid.
Acetazolamide The therapeutic efficacy of Acetazolamide can be decreased when used in combination with Gamolenic acid.
Diazepam The therapeutic efficacy of Diazepam can be decreased when used in combination with Gamolenic acid.
Phensuximide The therapeutic efficacy of Phensuximide can be decreased when used in combination with Gamolenic acid.
Progabide The therapeutic efficacy of Progabide can be decreased when used in combination with Gamolenic acid.
Methylphenobarbital The therapeutic efficacy of Methylphenobarbital can be decreased when used in combination with Gamolenic acid.
Tiagabine The therapeutic efficacy of Tiagabine can be decreased when used in combination with Gamolenic acid.
Zonisamide The therapeutic efficacy of Zonisamide can be decreased when used in combination with Gamolenic acid.
Felbamate The therapeutic efficacy of Felbamate can be decreased when used in combination with Gamolenic acid.
Zaleplon The therapeutic efficacy of Zaleplon can be decreased when used in combination with Gamolenic acid.
Gabapentin The therapeutic efficacy of Gabapentin can be decreased when used in combination with Gamolenic acid.
Clonazepam The therapeutic efficacy of Clonazepam can be decreased when used in combination with Gamolenic acid.
Vigabatrin The therapeutic efficacy of Vigabatrin can be decreased when used in combination with Gamolenic acid.
Phenacemide The therapeutic efficacy of Phenacemide can be decreased when used in combination with Gamolenic acid.
Thiamylal The therapeutic efficacy of Thiamylal can be decreased when used in combination with Gamolenic acid.
Phenobarbital The therapeutic efficacy of Phenobarbital can be decreased when used in combination with Gamolenic acid.
Levetiracetam The therapeutic efficacy of Levetiracetam can be decreased when used in combination with Gamolenic acid.
Estazolam The therapeutic efficacy of Estazolam can be decreased when used in combination with Gamolenic acid.
Fosphenytoin The therapeutic efficacy of Fosphenytoin can be decreased when used in combination with Gamolenic acid.
Amobarbital The therapeutic efficacy of Amobarbital can be decreased when used in combination with Gamolenic acid.
Hexobarbital The therapeutic efficacy of Hexobarbital can be decreased when used in combination with Gamolenic acid.
Barbital The therapeutic efficacy of Barbital can be decreased when used in combination with Gamolenic acid.
Delorazepam The therapeutic efficacy of Delorazepam can be decreased when used in combination with Gamolenic acid.
Nitrazepam The therapeutic efficacy of Nitrazepam can be decreased when used in combination with Gamolenic acid.
7-Nitroindazole The therapeutic efficacy of 7-Nitroindazole can be decreased when used in combination with Gamolenic acid.
Valpromide The therapeutic efficacy of Valpromide can be decreased when used in combination with Gamolenic acid.
Flunarizine The therapeutic efficacy of Flunarizine can be decreased when used in combination with Gamolenic acid.
Ezogabine The therapeutic efficacy of Ezogabine can be decreased when used in combination with Gamolenic acid.
Methsuximide The therapeutic efficacy of Methsuximide can be decreased when used in combination with Gamolenic acid.
Brivaracetam The therapeutic efficacy of Brivaracetam can be decreased when used in combination with Gamolenic acid.
Rufinamide The therapeutic efficacy of Rufinamide can be decreased when used in combination with Gamolenic acid.
Lacosamide The therapeutic efficacy of Lacosamide can be decreased when used in combination with Gamolenic acid.
Remacemide The therapeutic efficacy of Remacemide can be decreased when used in combination with Gamolenic acid.
Clomethiazole The therapeutic efficacy of Clomethiazole can be decreased when used in combination with Gamolenic acid.
Deramciclane The therapeutic efficacy of Deramciclane can be decreased when used in combination with Gamolenic acid.
Tramiprosate The therapeutic efficacy of Tramiprosate can be decreased when used in combination with Gamolenic acid.
Gaboxadol The therapeutic efficacy of Gaboxadol can be decreased when used in combination with Gamolenic acid.
Sulthiame The therapeutic efficacy of Sulthiame can be decreased when used in combination with Gamolenic acid.
Perampanel The therapeutic efficacy of Perampanel can be decreased when used in combination with Gamolenic acid.
Ifenprodil The therapeutic efficacy of Ifenprodil can be decreased when used in combination with Gamolenic acid.
Barbexaclone The therapeutic efficacy of Barbexaclone can be decreased when used in combination with Gamolenic acid.
Beclamide The therapeutic efficacy of Beclamide can be decreased when used in combination with Gamolenic acid.
Cannabidiol The therapeutic efficacy of Cannabidiol can be decreased when used in combination with Gamolenic acid.
Paraldehyde The therapeutic efficacy of Paraldehyde can be decreased when used in combination with Gamolenic acid.
Stiripentol The therapeutic efficacy of Stiripentol can be decreased when used in combination with Gamolenic acid.
Eslicarbazepine acetate The therapeutic efficacy of Eslicarbazepine acetate can be decreased when used in combination with Gamolenic acid.
Doramectin The therapeutic efficacy of Doramectin can be decreased when used in combination with Gamolenic acid.
Tiletamine The therapeutic efficacy of Tiletamine can be decreased when used in combination with Gamolenic acid.
Brexanolone The therapeutic efficacy of Brexanolone can be decreased when used in combination with Gamolenic acid.
Etiracetam The therapeutic efficacy of Etiracetam can be decreased when used in combination with Gamolenic acid.
Vinpocetine The therapeutic efficacy of Vinpocetine can be decreased when used in combination with Gamolenic acid.
Carisbamate The therapeutic efficacy of Carisbamate can be decreased when used in combination with Gamolenic acid.
Pheneturide The therapeutic efficacy of Pheneturide can be decreased when used in combination with Gamolenic acid.
Neocitrullamon The therapeutic efficacy of Neocitrullamon can be decreased when used in combination with Gamolenic acid.
Medazepam The therapeutic efficacy of Medazepam can be decreased when used in combination with Gamolenic acid.
Phenibut The therapeutic efficacy of Phenibut can be decreased when used in combination with Gamolenic acid.
Ethadione The therapeutic efficacy of Ethadione can be decreased when used in combination with Gamolenic acid.
Cannabidivarin The therapeutic efficacy of Cannabidivarin can be decreased when used in combination with Gamolenic acid.
Eslicarbazepine The therapeutic efficacy of Eslicarbazepine can be decreased when used in combination with Gamolenic acid.
JNJ-26489112 The therapeutic efficacy of JNJ-26489112 can be decreased when used in combination with Gamolenic acid.
Cenobamate The therapeutic efficacy of Cenobamate can be decreased when used in combination with Gamolenic acid.
Amifampridine The risk or severity of seizure can be increased when Gamolenic acid is combined with Amifampridine.
Dalfampridine The risk or severity of seizure can be increased when Gamolenic acid is combined with Dalfampridine.
Bupropion The risk or severity of seizure can be increased when Bupropion is combined with Gamolenic acid.
Fenfluramine The therapeutic efficacy of Fenfluramine can be decreased when used in combination with Gamolenic acid.
Ganaxolone The therapeutic efficacy of Ganaxolone can be decreased when used in combination with Gamolenic acid.
Hydroxychloroquine The risk or severity of seizure can be increased when Hydroxychloroquine is combined with Gamolenic acid.

Referensi & Sumber

Artikel (PubMed)
  • PMID: 27083549
    Sergeant S, Rahbar E, Chilton FH: Gamma-linolenic acid, Dihommo-gamma linolenic, Eicosanoids and Inflammatory Processes. Eur J Pharmacol. 2016 Aug 15;785:77-86. doi: 10.1016/j.ejphar.2016.04.020. Epub 2016 Apr 12.
  • PMID: 9732298
    Fan YY, Chapkin RS: Importance of dietary gamma-linolenic acid in human health and nutrition. J Nutr. 1998 Sep;128(9):1411-4. doi: 10.1093/jn/128.9.1411.
  • PMID: 23074118
    Kim DH, Yoo TH, Lee SH, Kang HY, Nam BY, Kwak SJ, Kim JK, Park JT, Han SH, Kang SW: Gamma linolenic acid exerts anti-inflammatory and anti-fibrotic effects in diabetic nephropathy. Yonsei Med J. 2012 Nov 1;53(6):1165-75. doi: 10.3349/ymj.2012.53.6.1165.
  • PMID: 26101612
    Chamberlin AJ, Bauer JE: Dietary gamma-linolenic acid supports arachidonic acid accretion and associated Delta-5 desaturase activity in feline uterine but not ovarian tissues. J Nutr Sci. 2014 Oct 13;3:e43. doi: 10.1017/jns.2014.41. eCollection 2014.
  • PMID: 8753781
    Hrelia S, Bordoni A, Biagi P, Rossi CA, Bernardi L, Horrobin DF, Pession A: gamma-Linolenic acid supplementation can affect cancer cell proliferation via modification of fatty acid composition. Biochem Biophys Res Commun. 1996 Aug 14;225(2):441-7. doi: 10.1006/bbrc.1996.1192.
  • PMID: 9932142
    Kruger MC, Coetzer H, de Winter R, Gericke G, van Papendorp DH: Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Aging (Milano). 1998 Oct;10(5):385-94.
  • PMID: 24435467
    Simon D, Eng PA, Borelli S, Kagi R, Zimmermann C, Zahner C, Drewe J, Hess L, Ferrari G, Lautenschlager S, Wuthrich B, Schmid-Grendelmeier P: Gamma-linolenic acid levels correlate with clinical efficacy of evening primrose oil in patients with atopic dermatitis. Adv Ther. 2014 Feb;31(2):180-8. doi: 10.1007/s12325-014-0093-0. Epub 2014 Jan 17.

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