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

General Information of Drug (ID: DMEZA0T)

• Drug Name: PF-3409409 Drug Info
• Synonyms: CHEMBL552338; PF-3409409; SCHEMBL5888234; BDBM50297077

Indication

Disease Entry	ICD 11	Status	REF
Attention deficit hyperactivity disorder	6A05.Z	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 44517677
  TTD Drug ID: DMEZA0T

Molecule-Related Drug Atlas

Drug(s) Targeting Muscarinic acetylcholine receptor M4 (CHRM4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[2]
Methacholine Chloride	DMGS4QH	Asthma	CA23	Approved	[3]
Tropicamide	DM1D90W	Mydriasis	LA11.62	Approved	[4]
Diphenidol	DMHPWOM	Nausea	MD90	Approved	[5]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[6]
A-987306	DMU34BK	Discovery agent	N.A.	Investigative	[7]
ISOCLOZAPINE	DM52CPU	Discovery agent	N.A.	Investigative	[8]
FLUMEZAPINE	DMW0HOG	Discovery agent	N.A.	Investigative	[9]
ISOLOXAPINE	DMH1BN4	Discovery agent	N.A.	Investigative	[10]
Acetic acid 8-aza-bicyclo[3.2.1]oct-6-yl ester	DMVEH40	Discovery agent	N.A.	Investigative	[3]

Drug(s) Targeting Norepinephrine transporter (NET)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[11]
Amitriptyline	DMK7F9S	Depression	6A70-6A7Z	Approved	[12]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[13]
Desipramine	DMT2FDC	Attention deficit hyperactivity disorder	6A05.Z	Approved	[11]
Cocaine	DMSOX7I	Anaesthesia	9A78.6	Approved	[14]
Bupropion	DM5PCS7	Depression	6A70-6A7Z	Approved	[15]
Tapentadol hydrochloride	DMXLSH3	Acute pain	MG31	Approved	[16]
Venlafaxine	DMR6QH0	Anxiety disorder	6B00-6B0Z	Approved	[15]
Trimipramine	DM1SC8M	Major depressive disorder	6A70.3	Approved	[17]
Duloxetine	DM9BI7M	Depression	6A70-6A7Z	Approved	[18]

Drug(s) Targeting Serotonin transporter (SERT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[11]
Amitriptyline	DMK7F9S	Depression	6A70-6A7Z	Approved	[12]
Fluoxetine	DM3PD2C	Bipolar depression		Approved	[19]
Vortioxetine	DM6F1PU	Major depressive disorder	6A70.3	Approved	[20]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[21]
Cocaine	DMSOX7I	Anaesthesia	9A78.6	Approved	[14]
Bupropion	DM5PCS7	Depression	6A70-6A7Z	Approved	[15]
Citalopram	DM2G9AE	Acute coronary syndrome	BA41	Approved	[19]
Nortriptyline	DM4KDYJ	Depression	6A70-6A7Z	Approved	[19]
Trazodone	DMK1GBJ	Depression	6A70-6A7Z	Approved	[19]

Drug(s) Targeting Dopamine transporter (DAT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cocaine	DMSOX7I	Anaesthesia	9A78.6	Approved	[14]
Dasotraline	DMLDQFV	Attention deficit hyperactivity disorder	6A05.Z	Approved	[22]
Methylphenidate	DM7SJD6	Attention deficit hyperactivity disorder	6A05.Z	Approved	[23]
Modafinil	DMYILBE	Malignant glioma	2A00.0	Approved	[19]
Phenmetrazine	DMXYTN9	Obesity	5B81	Approved	[24]
Ioflupane i-123	DMNARJT	Parkinson disease	8A00.0	Approved	[25]
DEXMETHYLPHENIDATE HYDROCHLORIDE	DM8WBAH	Attention deficit hyperactivity disorder	6A05.Z	Approved	[26]
Altropane	DMO9WDS	Attention deficit hyperactivity disorder	6A05.Z	Approved	[27]
Amitifadine	DMS1X67	Obesity	5B81	Phase 3	[28]
NAV5001	DMRSI1M	Dementia	6D80-6D86	Phase 3	[27]

Drug(s) Targeting Muscarinic acetylcholine receptor M5 (CHRM5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Promazine	DMZAL7W	Acute intermittent hepatic porphyria	5C58.11	Approved	[29]
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[2]
Pilocarpine	DMV9ADG	Glaucoma/ocular hypertension	9C61	Approved	[30]
Anisodine	DMNOSWU	Central and peripheral nervous disease	8A04-8E7Z	Approved	[31]
Atropine	DMEN6X7	Organophosphate poisoning	NE6Z	Approved	[32]
Propiverine	DMUWBIJ	Urinary incontinence	MF50.2	Approved	[33]
Umeclidinium	DM4E8O9	Chronic obstructive pulmonary disease	CA22	Approved	[34]
Cimetropium bromide	DMZHPNE	Gastric motility disorder	DA21	Approved	[35]
Butylscopolamine	DMZKXB7	Dysmenorrhea	GA34.3	Approved	[36]
Trospium	DMX6RTG	Overactive bladder	GC50.0	Approved	[37]

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]
Muscarinic acetylcholine receptor M4 (CHRM4)	TTQ3JTF	ACM4_HUMAN	Inhibitor	[1]
Muscarinic acetylcholine receptor M5 (CHRM5)	TTH18TF	ACM5_HUMAN	Inhibitor	[1]
Norepinephrine transporter (NET)	TTAWNKZ	SC6A2_HUMAN	Inhibitor	[1]
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Inhibitor	[1]

References

• [1] Design, synthesis and evaluation of N-[(3S)-pyrrolidin-3-yl]benzamides as selective noradrenaline reuptake inhibitors: CNS penetration in a more po... Bioorg Med Chem Lett. 2009 Aug 15;19(16):4579-83.
• [2] Design, synthesis, and neurochemical evaluation of 5-(3-alkyl-1,2,4- oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists. J Med Chem. 1993 Apr 2;36(7):842-7.
• [3] 6beta-Acetoxynortropane: a potent muscarinic agonist with apparent selectivity toward M2-receptors. J Med Chem. 1998 Jun 4;41(12):2047-55.
• [4] The muscarinic receptor antagonist tropicamide suppresses tremulous jaw movements in a rodent model of parkinsonian tremor: possible role of M4 rec... Psychopharmacology (Berl). 2007 Oct;194(3):347-59.
• [5] Diphenidol-related diamines as novel muscarinic M4 receptor antagonists. Bioorg Med Chem Lett. 2008 May 1;18(9):2972-6.
• [6] 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.
• [7] cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain... J Med Chem. 2008 Nov 27;51(22):7094-8.
• [8] Chloro-substituted, sterically hindered 5,11-dicarbo analogues of clozapine as potential chiral antipsychotic agents. J Med Chem. 1990 Feb;33(2):809-14.
• [9] Synthesis and pharmacological evaluation of a series of 4-piperazinylpyrazolo[3,4-b]- and -[4,3-b][1,5]benzodiazepines as potential anxiolytics. J Med Chem. 1989 Dec;32(12):2573-82.
• [10] Synthesis of clozapine analogues and their affinity for clozapine and spiroperidol binding sites in rat brain. J Med Chem. 1981 Sep;24(9):1021-6.
• [11] Augmentation effect of combination therapy of aripiprazole and antidepressants on forced swimming test in mice. Psychopharmacology (Berl). 2009 Sep;206(1):97-107.
• [12] Treatment of comorbid pain with serotonin norepinephrine reuptake inhibitors. CNS Spectr. 2008 Jul;13(7 Suppl 11):22-6.
• [13] Invivo antioxidant status: a putative target of antidepressant action. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Mar 17;33(2):220-8.
• [14] 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.
• [15] Clinically relevant drug interactions with new generation antidepressants and antipsychotics. Ther Umsch. 2009 Jun;66(6):485-92.
• [16] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [17] Antidepressants suppress production of the Th1 cytokine interferon-gamma, independent of monoamine transporter blockade. Eur Neuropsychopharmacol. 2006 Oct;16(7):481-90.
• [18] Multi-target therapeutics: when the whole is greater than the sum of the parts. Drug Discov Today. 2007 Jan;12(1-2):34-42.
• [19] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [20] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [21] Psychopharmacological treatment of dermatological patients--when simply talking does not help. J Dtsch Dermatol Ges. 2007 Dec;5(12):1101-6.
• [22] 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.
• [23] 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.
• [24] 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.
• [25] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [26] 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.
• [27] Rapid detection of Parkinson's disease by SPECT with altropane: a selective ligand for dopamine transporters. Synapse. 1998 Jun;29(2):128-41.
• [28] 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).
• [29] Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12.
• [30] Retinoic acid prevents virus-induced airway hyperreactivity and M2 receptor dysfunction via anti-inflammatory and antiviral effects. Am J Physiol Lung Cell Mol Physiol. 2009 Aug;297(2):L340-6.
• [31] Medicinal plants in therapy. Bull World Health Organ. 1985;63(6):965-81.
• [32] Additive protective effects of donepezil and nicotine against salsolinol-induced cytotoxicity in SH-SY5Y cells. Neurotox Res. 2009 Oct;16(3):194-204.
• [33] Affinity profiles of various muscarinic antagonists for cloned human muscarinic acetylcholine receptor (mAChR) subtypes and mAChRs in rat heart and submandibular gland. Life Sci. 1999;64(25):2351-8.
• [34] 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: 7354).
• [35] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [36] Comparison of pharmacological effects of L- and DL-n-butyl-scopolamine in rat uterus. Yao Xue Xue Bao. 1994;29(1):24-7.
• [37] Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.