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

General Information of Drug (ID: DM6L5VO)

• Drug Name: Methsuximide Drug Info
• Synonyms: Celontin; Mesuximid; Mesuximida; Mesuximide; Mesuximidum; Methsuximid; Metosuccimmide; Metsuccimide; Petinutin; Methsuximide [BAN]; Metosuccimmide [DCIT]; PM 396; Alpha-Methylphensuximide; Celontin (TN); Mesuximida [INN-Spanish]; Mesuximide (INN); Mesuximidum [INN-Latin]; Methsuximide (USP); Petinutin (TN); Alpha-Methyl-alpha-phenyl N-methyl succinimide; N,2-Dimethyl-2-phenylsuccinimide; N-Methyl-alpha-methyl-alpha-phenylsuccinimide; (+-)-N,2-Dimethyl-2-phenylsuccinimide; (RS)-1,3-Dimethyl-3-phenyl-2,5-pyrrolidindion; 1,3-Dimethyl-3-phenyl-2,5-dioxopyrrolidine; 1,3-Dimethyl-3-phenyl-2,5-pyrrolidinedione; 1,3-Dimethyl-3-phenyl-pyrrolidin-2,5-dione; 1,3-Dimethyl-3-phenylsuccinimide; 1,3-dimethyl-3-phenylpyrrolidine-2,5-dione

Indication

Disease Entry	ICD 11	Status	REF
Absence epilepsy		Approved	[1]
Epilepsy	8A60-8A68	Approved	[1]
Epileptic seizures	8A61-8A6Z	Approved	[2]

• Therapeutic Class: Anticonvulsants
• Cross-matching ID:
  PubChem CID: 6476
  ChEBI ID: CHEBI:6846
  CAS Number: CAS 77-41-8
  TTD Drug ID: DM6L5VO
  INTEDE Drug ID: DR1050
  ACDINA Drug ID: D00415

Molecule-Related Drug Atlas

Drug(s) Targeting Voltage-gated calcium channel alpha Cav3.1 (CACNA1G)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[5]
Ethosuximide	DMDZ9LT	Epilepsy	8A60-8A68	Approved	[6]
Trimethadione	DM0Q8MZ	Absence epilepsy		Approved	[7]
Paramethadione	DMR5ZUP	Absence epilepsy		Approved	[7]
Penfluridol	DMG1DTE	Schizophrenia	6A20	Approved	[8]
PD-200390	DMPW28M	Insomnia	7A00-7A0Z	Phase 2	[9]
NGD 94-1	DMM1Y8F	Schizophrenia	6A20	Phase 1	[8]
ML218	DM3D21X	Discovery agent	N.A.	Investigative	[10]
KYS-05001	DM3MID9	Discovery agent	N.A.	Investigative	[11]
KYS-05077	DMHW40F	Discovery agent	N.A.	Investigative	[12]

Drug(s) Metabolized By Mephenytoin 4-hydroxylase (CYP2C19)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[13]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[14]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[15]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[16]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[17]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[18]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[19]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[20]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[21]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[22]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Voltage-gated calcium channel alpha Cav3.1 (CACNA1G)	TT729IR	CAC1G_HUMAN	Blocker	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Mephenytoin 4-hydroxylase (CYP2C19) Main DME	DEGTFWK	CP2CJ_HUMAN	Substrate	[4]

References

• [1] Methsuximide FDA Label
• [2] 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: 7228).
• [3] Block of cloned human T-type calcium channels by succinimide antiepileptic drugs. Mol Pharmacol. 2001 Nov;60(5):1121-32.
• [4] The role of S-mephenytoin hydroxylase (CYP2C19) in the metabolism of the antimalarial biguanides. Br J Clin Pharmacol. 1995 Apr;39(4):441-4.
• [5] Mechanism of tissue-selective drug action in the cardiovascular system. Mol Interv. 2005 Apr;5(2):84-93.
• [6] Maladaptive homeostatic plasticity in a rodent model of central pain syndrome: thalamic hyperexcitability after spinothalamic tract lesions. J Neurosci. 2008 Nov 12;28(46):11959-69.
• [7] Prophylactic and therapeutic functions of T-type calcium blockers against noise-induced hearing loss. Hear Res. 2007 Apr;226(1-2):52-60.
• [8] Differential inhibition of T-type calcium channels by neuroleptics. J Neurosci. 2002 Jan 15;22(2):396-403.
• [9] Pfizer. Product Development Pipeline. March 31 2009.
• [10] The Discovery and Characterization of ML218: A Novel, Centrally Active T-Type Calcium Channel Inhibitor with Robust Effects in STN Neurons and in a Rodent Model of Parkinson's Disease. ACS Chem Neurosci. 2011 Dec 21;2(12):730-742.
• [11] Discovery of potent T-type calcium channel blocker. Bioorg Med Chem Lett. 2007 Nov 1;17(21):5740-3.
• [12] Synthesis and biological evaluation of novel T-type calcium channel blockers. Bioorg Med Chem Lett. 2007 Jan 15;17(2):471-5.
• [13] High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin. Hepatogastroenterology. 2003 Nov-Dec;50(54):2274-8.
• [14] Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
• [15] Cytochrome P450 pharmacogenetics and cancer. Oncogene. 2006 Mar 13;25(11):1679-91.
• [16] CYP2C19*17 is associated with decreased breast cancer risk. Breast Cancer Res Treat. 2009 May;115(2):391-6.
• [17] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [18] Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21.
• [19] Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
• [20] A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
• [21] Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33.
• [22] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.