Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM6T924)

• Drug Name: Gabapentin Drug Info
• Synonyms: Aclonium; GBN; Gabapen; Gabapentina; Gabapentine; Gabapentinium; Gabapentino; Gabapentinum; Gabapetin; Neurontin; Serada; Vultin; Apotex brand of gabapentin; Aventis brand of gabapentin; Gabapentin GR; Gabapentin Hexal; Gabapentin Stada; Gabapentino [Spanish]; Hexal brand of gabapentin; Novopharm brand of gabapentin; Parke Davis brand of gabapentin; Pfizer brand of gabapentin; Pharmascience brand of gabapentin; Ratiopharm brand of gabapentin; Stadapharm brand of gabapentin; GOE 2450; Go 3450; Apo-Gabapentin; DDS-2003; DM-1796; DM-5689; G-154; Gabapentin (Neurontin); Gabapentin-ratiopharm; Gabapentine [INN-French]; Gabapentino [INN-Spanish]; Gabapentinum [INN-Latin]; Goe-3450; Neurontin (TN); Novo-Gabapentin; PMS-Gabapentin; Warner-Lambert brand of gabapentin; Gabapentin [USAN:INN:BAN]; [1-(AMINOMETHYL)CYCLOHEXYL]ACETIC ACID; Gabapentin (JAN/USAN/INN); 1-(Aminomethyl)-cyclohexaneacetic acid; 1-(Aminomethyl)cyclohexaneacetic acid; 2-[1-(aminomethyl)cyclohexyl]acetic acid

Indication

Disease Entry	ICD 11	Status	REF
Complex partial seizure	8A68.0	Approved	[1] , [2]
Solid tumour/cancer	2A00-2F9Z	Phase 3	[1] , [3]

• Therapeutic Class: Analgesics
• Cross-matching ID:
  PubChem CID: 3446
  ChEBI ID: CHEBI:42797
  CAS Number: CAS 60142-96-3
  TTD Drug ID: DM6T924
  VARIDT Drug ID: DR00217
  ACDINA Drug ID: D00296

Molecule-Related Drug Atlas

Drug(s) Transported By Organic cation transporter 2 (SLC22A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[8]
Cisplatin	DMRHGI9	Solid tumour/cancer	2A00-2F9Z	Approved	[9]
Oxaliplatin	DMQNWRD	Colorectal cancer	2B91.Z	Approved	[10]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[11]
Dopamine	DMPGUCF	Parkinson disease	8A00.0	Approved	[12]
Propranolol	DM79NTF	Migraine	8A80	Approved	[13]
Ergotidine	DM78IME	Respiratory allergy	4A80	Approved	[14]
Metformin	DM89QE1	Type-2 diabetes	5A11	Approved	[15]
Clonidine	DM6RZ9Q	Hypertension	BA00-BA04	Approved	[13]
Ranitidine	DM0GUSX	Peptic ulcer	DA61	Approved	[16]

Drug(s) Transported By Organic cation/carnitine transporter 1 (SLC22A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Verapamil	DMA7PEW	Hypertension	BA00-BA04	Approved	[17]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[17]
Cytarabine	DMZD5QR	Acute lymphoblastic leukaemia	2A85	Approved	[18]
Levacecarnine HCL	DMJBOCR	Cognitive impairment	6D71	Approved	[19]
Ipratropium	DMFQ320	Obstructive lung disease	CA22.Z	Approved	[20]
[14C]TEA	DM6SFYH	Discovery agent	N.A.	Investigative	[21]

Drug(s) Transported By L-type amino acid transporter 1 (SLC7A5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-glutamine	DM69G8X	Short bowel syndrome	KB89.1	Approved	[22]
Levodopa	DMN3E57	Parkinson disease	8A00.0	Approved	[23]
Pregabalin	DMDVP3B	Chronic obstructive pulmonary disease	CA22	Approved	[24]
L-leucine	DMQHN7I	Discovery agent	N.A.	Investigative	[22]

Drug(s) Targeting Gamma-aminobutyric acid B receptor (GABBR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Gamma hydroxybutyric acid	DMGBKVD	Narcolepsy	7A20	Approved	[25]
Baclofen	DM0QV1J	Multiple sclerosis	8A40	Approved	[26]
Progabide	DM671NG	Depression	6A70-6A7Z	Approved	[27]
Arbaclofen placarbil	DMO628K	Fragile X syndrome	LD55	Phase 3	[28]
[3H](R)-(-)-baclofen	DMLRHM5	Multiple sclerosis	8A40	Phase 3	[29]
Arabaclofen	DMZB9RI	Fragile X syndrome	LD55	Phase 3	[30]
GSK683699	DMTW79H	Inflammatory bowel disease	DD72	Phase 2	[31]
SGS742	DM5XYFH	Schizophrenia	6A20	Phase 2	[32]
SSTarbaclofen	DMRGTZ2	Autism spectrum disorder	6A02	Phase 2	[33]
ASP8062	DMR1MIV	Fibromyalgia	MG30.01	Phase 2	[34]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Gamma-aminobutyric acid B receptor (GABBR)	TTDCVZW	GABR1_HUMAN; GABR2_HUMAN	Antagonist	[4]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
L-type amino acid transporter 1 (SLC7A5)	DT48T0N	LAT1_HUMAN	Substrate	[5]
Organic cation/carnitine transporter 1 (SLC22A4)	DT2EG60	S22A4_HUMAN	Substrate	[6]
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[7]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5483).
• [2] Use of second-generation antiepileptic drugs in the pediatric population. Paediatr Drugs. 2008;10(4):217-54.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Gabapentin increases a tonic inhibitory conductance in hippocampal pyramidal neurons. Anesthesiology. 2006 Aug;105(2):325-33.
• [5] Transport of gabapentin by LAT1 (SLC7A5). Biochem Pharmacol. 2013 Jun 1;85(11):1672-83.
• [6] Effects of genetic variation in the novel organic cation transporter, OCTN1, on the renal clearance of gabapentin. Clin Pharmacol Ther. 2008 Mar;83(3):416-21.
• [7] Clinical pharmacokinetic drug interaction studies of gabapentin enacarbil, a novel transported prodrug of gabapentin, with naproxen and cimetidine. Br J Clin Pharmacol. 2010 May;69(5):498-507.
• [8] Are organic cation transporters capable of transporting prostaglandins? Naunyn Schmiedebergs Arch Pharmacol. 2005 Aug;372(2):125-30.
• [9] Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2. Am J Pathol. 2005 Dec;167(6):1477-84.
• [10] Relevance of copper transporter 1 and organic cation transporters 1-3 for oxaliplatin uptake and drug resistance in colorectal cancer cells. Metallomics. 2018 Mar 1;10(3):414-425.
• [11] Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol. 1997 Jul;16(7):871-81.
• [12] Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain. Neuropharmacology. 2006 Jun;50(8):941-52.
• [13] Influx Transport of Cationic Drug at the Blood-Retinal Barrier: Impact on the Retinal Delivery of Neuroprotectants. Biol Pharm Bull. 2017;40(8):1139-1145.
• [14] The organic cation transporters (OCT1, OCT2, EMT) and the plasma membrane monoamine transporter (PMAT) show differential distribution and cyclic expression pattern in human endometrium and early pregnancy decidua. Mol Reprod Dev. 2007 Oct;74(10):1303-11.
• [15] Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet. 2005 Oct;20(5):379-86.
• [16] A species difference in the transport activities of H2 receptor antagonists by rat and human renal organic anion and cation transporters. J Pharmacol Exp Ther. 2005 Oct;315(1):337-45.
• [17] Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73.
• [18] OCTN1 Is a High-Affinity Carrier of Nucleoside Analogues. Cancer Res. 2017 Apr 15;77(8):2102-2111.
• [19] Spontaneous development of intestinal and colonic atrophy and inflammation in the carnitine-deficient jvs (OCTN2(-/-)) mice. Mol Genet Metab. 2007 Dec;92(4):315-24.
• [20] Transport of ipratropium, an anti-chronic obstructive pulmonary disease drug, is mediated by organic cation/carnitine transporters in human bronchial epithelial cells: implications for carrier-mediated pulmonary absorption. Mol Pharm. 2010 Feb 1;7(1):187-95.
• [21] Functional effects of protein sequence polymorphisms in the organic cation/ergothioneine transporter OCTN1 (SLC22A4). Pharmacogenet Genomics. 2007 Sep;17(9):773-82.
• [22] Bidirectional transport of amino acids regulates mTOR and autophagy. Cell. 2009 Feb 6;136(3):521-34.
• [23] Modulation of LAT1 (SLC7A5) transporter activity and stability by membrane cholesterol. Sci Rep. 2017 Mar 8;7:43580.
• [24] Transport of Pregabalin Via L-Type Amino Acid Transporter 1 (SLC7A5) in Human Brain Capillary Endothelial Cell Line. Pharm Res. 2018 Oct 29;35(12):246.
• [25] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [26] Synthesis and pharmacology of the baclofen homologues 5-amino-4-(4-chlorophenyl)pentanoic acid and the R- and S-enantiomers of 5-amino-3-(4-chlorop... J Med Chem. 1999 Jun 3;42(11):2053-9.
• [27] Interactions between dopamine and GABA in the control of ambulatory activity and neophobia in the mouse. Pharmacol Biochem Behav. 1998 Jan;59(1):239-47.
• [28] Arbaclofen placarbil, a novel R-baclofen prodrug: improved absorption, distribution, metabolism, and elimination properties compared with R-baclofen.J Pharmacol Exp Ther.2009 Sep;330(3):911-21.
• [29] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 242).
• [30] Impact of acamprosate on behavior and brain-derived neurotrophic factor: an open-label study in youth with fragile X syndrome. Psychopharmacology (Berl). 2013 Jul;228(1):75-84.
• [31] 3-Thienyl- and 3-furylaminobutyric acids. Synthesis and binding GABAB receptor studies. J Med Chem. 1991 Aug;34(8):2557-60.
• [32] SGS742: the first GABA(B) receptor antagonist in clinical trials. Biochem Pharmacol. 2004 Oct 15;68(8):1479-87.
• [33] Reversal of disease-related pathologies in the fragile X mouse model by selective activation of GABAB receptors with arbaclofen. Sci Transl Med. 2012 Sep 19;4(152):152ra128.
• [34] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)