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

General Information of Drug (ID: DMDUGZS)

• Drug Name: (2S,3S)-2-Phenyl-3,5,5-trimethylmorpholin-2-ol Drug Info
• Synonyms: CHEMBL1173274; (2S,3S)-2-Phenyl-3,5,5-trimethylmorpholin-2-ol; SCHEMBL15007461; NGHJSSNVKXEBAB-GXFFZTMASA-N

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 46837647
  TTD Drug ID: DMDUGZS

Molecule-Related Drug Atlas

Drug(s) Targeting Norepinephrine transporter (NET)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[2]
Amitriptyline	DMK7F9S	Depression	6A70-6A7Z	Approved	[3]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[4]
Desipramine	DMT2FDC	Attention deficit hyperactivity disorder	6A05.Z	Approved	[2]
Cocaine	DMSOX7I	Anaesthesia	9A78.6	Approved	[5]
Bupropion	DM5PCS7	Depression	6A70-6A7Z	Approved	[6]
Tapentadol hydrochloride	DMXLSH3	Acute pain	MG31	Approved	[7]
Venlafaxine	DMR6QH0	Anxiety disorder	6B00-6B0Z	Approved	[6]
Trimipramine	DM1SC8M	Major depressive disorder	6A70.3	Approved	[8]
Duloxetine	DM9BI7M	Depression	6A70-6A7Z	Approved	[9]

Drug(s) Targeting Dopamine transporter (DAT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cocaine	DMSOX7I	Anaesthesia	9A78.6	Approved	[5]
Dasotraline	DMLDQFV	Attention deficit hyperactivity disorder	6A05.Z	Approved	[10]
Methylphenidate	DM7SJD6	Attention deficit hyperactivity disorder	6A05.Z	Approved	[11]
Modafinil	DMYILBE	Malignant glioma	2A00.0	Approved	[12]
Phenmetrazine	DMXYTN9	Obesity	5B81	Approved	[13]
Ioflupane i-123	DMNARJT	Parkinson disease	8A00.0	Approved	[14]
DEXMETHYLPHENIDATE HYDROCHLORIDE	DM8WBAH	Attention deficit hyperactivity disorder	6A05.Z	Approved	[15]
Altropane	DMO9WDS	Attention deficit hyperactivity disorder	6A05.Z	Approved	[16]
Amitifadine	DMS1X67	Obesity	5B81	Phase 3	[17]
NAV5001	DMRSI1M	Dementia	6D80-6D86	Phase 3	[16]

Drug(s) Targeting Neuronal acetylcholine receptor alpha-4 (CHRNA4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Trimethaphan	DMHF4IQ	Aneurysm	BD51.Z	Approved	[18]
Pentolinium	DM38VYQ	Hypotension	BA20-BA21	Approved	[19]
CYTISINE	DMUF0BJ	Tobacco dependence	6C4A.2	Phase 3	[20]
ABT-594	DMGMBCW	N. A.	N. A.	Discontinued in Phase 2	[21]
ABT-418	DMNP72I	Alzheimer disease	8A20	Discontinued in Phase 2	[22]
HOMOEPIBATIDINE	DMHP9WV	N. A.	N. A.	Terminated	[20]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[23]
Barbituric acid derivative	DM2I19P	Discovery agent	N.A.	Investigative	[24]
(2S,3S)-2-(m-Tolyl)-3,5,5-trimethylmorpholin-2-ol	DMDUI8R	Discovery agent	N.A.	Investigative	[1]
BOLDINE	DMMVB5P	Discovery agent	N.A.	Investigative	[25]

Drug(s) Targeting Neuronal acetylcholine receptor beta-4 (CHRNB4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CYTISINE	DMUF0BJ	Tobacco dependence	6C4A.2	Phase 3	[26]
SIB-1553A	DM7XC0U	Alzheimer disease	8A20	Discontinued in Phase 2	[27]
HOMOEPIBATIDINE	DMHP9WV	N. A.	N. A.	Terminated	[20]
(2S,3S)-2-(m-Tolyl)-3,5,5-trimethylmorpholin-2-ol	DMDUI8R	Discovery agent	N.A.	Investigative	[1]
GCCSNPVCHLEHSNLC*	DMJ0ICN	Discovery agent	N.A.	Investigative	[28]
18-Methylaminocoronaridine	DMOYC0U	Discovery agent	N.A.	Investigative	[29]
15-nor-18-Methoxycornaridine	DMDKFGX	Discovery agent	N.A.	Investigative	[29]
2-Acetylaminoethyl 18-methoxycoronaridinate	DM9ZOX4	Discovery agent	N.A.	Investigative	[29]
N,N-Dimethylaminoethyl 18-methoxycoronaridinate	DMWJ2PM	Discovery agent	N.A.	Investigative	[29]
2-Methoxyethyl 18-methoxycoronaridinate	DM6X8GN	Discovery agent	N.A.	Investigative	[29]

Drug(s) Targeting Neuronal acetylcholine receptor beta-2 (CHRNB2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CYTISINE	DMUF0BJ	Tobacco dependence	6C4A.2	Phase 3	[20]
TC-5214	DM8AM60	Palmar hyperhidrosis	EE00.00	Phase 2	[30]
SUVN-911	DMLPBVF	Major depressive disorder	6A70.3	Phase 1	[31]
AZD-9684	DMHA5ME	Thrombosis	DB61-GB90	Discontinued in Phase 2	[32]
ABT-594	DMGMBCW	N. A.	N. A.	Discontinued in Phase 2	[21]
ABT-418	DMNP72I	Alzheimer disease	8A20	Discontinued in Phase 2	[33]
HOMOEPIBATIDINE	DMHP9WV	N. A.	N. A.	Terminated	[20]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[23]
(2S,3S)-2-(m-Tolyl)-3,5,5-trimethylmorpholin-2-ol	DMDUI8R	Discovery agent	N.A.	Investigative	[1]
BOLDINE	DMMVB5P	Discovery agent	N.A.	Investigative	[25]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dopamine transporter (DAT)	TTVBI8W	SC6A3_HUMAN	Inhibitor	[1]
Neuronal acetylcholine receptor alpha-4 (CHRNA4)	TT4H1MQ	ACHA4_HUMAN	Inhibitor	[1]
Neuronal acetylcholine receptor beta-2 (CHRNB2)	TT5KPZR	ACHB2_HUMAN	Inhibitor	[1]
Neuronal acetylcholine receptor beta-4 (CHRNB4)	TTTVAFQ	ACHB4_HUMAN	Inhibitor	[1]
Norepinephrine transporter (NET)	TTAWNKZ	SC6A2_HUMAN	Inhibitor	[1]

References

• [1] Synthesis and characterization of in vitro and in vivo profiles of hydroxybupropion analogues: aids to smoking cessation. J Med Chem. 2010 Jun 24;53(12):4731-48.
• [2] Augmentation effect of combination therapy of aripiprazole and antidepressants on forced swimming test in mice. Psychopharmacology (Berl). 2009 Sep;206(1):97-107.
• [3] Treatment of comorbid pain with serotonin norepinephrine reuptake inhibitors. CNS Spectr. 2008 Jul;13(7 Suppl 11):22-6.
• [4] Invivo antioxidant status: a putative target of antidepressant action. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Mar 17;33(2):220-8.
• [5] Differential involvement of the norepinephrine, serotonin and dopamine reuptake transporter proteins in cocaine-induced taste aversion. Pharmacol Biochem Behav. 2009 Jul;93(1):75-81.
• [6] Clinically relevant drug interactions with new generation antidepressants and antipsychotics. Ther Umsch. 2009 Jun;66(6):485-92.
• [7] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [8] Antidepressants suppress production of the Th1 cytokine interferon-gamma, independent of monoamine transporter blockade. Eur Neuropsychopharmacol. 2006 Oct;16(7):481-90.
• [9] Multi-target therapeutics: when the whole is greater than the sum of the parts. Drug Discov Today. 2007 Jan;12(1-2):34-42.
• [10] Dasotraline for the Treatment of Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Trial in Adults. Neuropsychopharmacology. 2015 Nov;40(12):2745-52.
• [11] Imaging the effects of methylphenidate on brain dopamine: new model on its therapeutic actions for attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005 Jun 1;57(11):1410-5.
• [12] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [13] Interaction of the anorectic medication, phendimetrazine, and its metabolites with monoamine transporters in rat brain. Eur J Pharmacol. 2002 Jun 28;447(1):51-7.
• [14] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [15] Synthesis and pharmacology of site-specific cocaine abuse treatment agents: restricted rotation analogues of methylphenidate. J Med Chem. 2007 May 31;50(11):2718-31.
• [16] Rapid detection of Parkinson's disease by SPECT with altropane: a selective ligand for dopamine transporters. Synapse. 1998 Jun;29(2):128-41.
• [17] 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: 927).
• [18] Mechanism of long-lasting block of ganglion nicotinic receptors by mono-ammonium compounds with long aliphatic chain. J Auton Nerv Syst. 1994 Aug;48(3):231-40.
• [19] Nicotinic and nonnicotinic receptor-mediated actions of vinblastine. Proc Soc Exp Biol Med. 1993 Jul;203(3):372-6.
• [20] Epibatidine isomers and analogues: structure-activity relationships. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5493-7.
• [21] The nicotinic acetylcholine receptor agonist ABT-594 increases FGF-2 expression in various rat brain regions. Neuroreport. 1999 Dec 16;10(18):3909-13.
• [22] (S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole (ABT 418): a novel cholinergic ligand with cognition-enhancing and anxiolytic activities: II. In vivo characterization. J Pharmacol Exp Ther. 1994 Jul;270(1):319-28.
• [23] Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 rec... J Med Chem. 2010 Sep 9;53(17):6386-97.
• [24] Whiting PJ: The GABAA receptor gene family: new opportunities for drug development. Curr Opin Drug Discov Devel. 2003 Sep;6(5):648-57.
• [25] Aporphine metho salts as neuronal nicotinic acetylcholine receptor blockers. Bioorg Med Chem. 2007 May 15;15(10):3368-72.
• [26] Deconstructing cytisine: The syntheses of (+/-)-cyfusine and (+/-)-cyclopropylcyfusine, fused ring analogs of cytisine. Bioorg Med Chem Lett. 2008 Apr 1;18(7):2316-9.
• [27] SIB-1553A, (+/-)-4-[[2-(1-methyl-2-pyrrolidinyl)ethyl]thio]phenol hydrochloride, a subtype-selective ligand for nicotinic acetylcholine receptors with putative cognitive-enhancing properties: effectson working and reference memory performances in aged rodents and nonhuman primates. J Pharmacol Exp Ther. 2001 Oct;299(1):297-306.
• [28] Neuronal nicotinic acetylcholine receptors: structural revelations, target identifications, and therapeutic inspirations. J Med Chem. 2005 Jul 28;48(15):4705-45.
• [29] Synthesis and biological evaluation of 18-methoxycoronaridine congeners. Potential antiaddiction agents. J Med Chem. 2003 Jun 19;46(13):2716-30.
• [30] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [31] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [32] Blockade and activation of the human neuronal nicotinic acetylcholine receptors by atracurium and laudanosine. Anesthesiology. 2001 Apr;94(4):643-51.
• [33] Nicotine, brain nicotinic receptors, and neuropsychiatric disorders. Arch Med Res. 2000 Mar-Apr;31(2):131-44.