Details of the Drug

General Information of Drug (ID: DMA9CSG)

• Drug Name: Beta-methoxyamphetamine
• Synonyms: 4-Methoxyamphetamine; p-Methoxyamphetamine; para-methoxyamphetamine; 1-(4-methoxyphenyl)propan-2-amine; 64-13-1; 1-p-Methoxyphenyl-2-propylamine; 1-p-Methoxyphenyl-2-aminopropane; paramethoxyamphetamine; beta-methoxyamphetamine; 1-(4-Methoxybenzyl)ethylamine; 2-Amino-1-(4'-methoxyphenyl)propane; p-Methoxy-alpha-methylphenethylamine; (+-)-p-Methoxyamphetamine; DEA No 7411; NSC 32757; 50505-80-1; 23239-32-9; DL-p-Methoxy-alpha-methylphenethylamine; (+-)-p-Methoxy-alpha-methylphenethylamine; Para-Methoxyamphetamine

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 165.23
  Topological Polar Surface Area (xlogp); 1.8
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 2
• Chemical Identifiers:
  Formula: C10H15NO
  IUPAC Name: 1-(4-methoxyphenyl)propan-2-amine
  Canonical SMILES: CC(CC1=CC=C(C=C1)OC)N
  InChI: InChI=1S/C10H15NO/c1-8(11)7-9-3-5-10(12-2)6-4-9/h3-6,8H,7,11H2,1-2H3
  InChIKey: NEGYEDYHPHMHGK-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 31721
  CAS Number: 64-13-1
  DrugBank ID: DB01472
  TTD ID: D0R7ZC
  INTEDE ID: DR0013

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adrenergic receptor alpha-1A (ADRA1A)	TTNGILX	ADA1A_HUMAN	Agonist	[1]
Adrenergic receptor alpha-1D (ADRA1D)	TT34BHT	ADA1D_HUMAN	Agonist	[1]
Adrenergic receptor alpha-2A (ADRA2A)	TTWG9A4	ADA2A_HUMAN	Agonist	[1]
Dopamine transporter (DAT)	TTVBI8W	SC6A3_HUMAN	Antagonist	[1]
Monoamine oxidase type A (MAO-A)	TT3WG5C	AOFA_HUMAN	Inhibitor	[1], [2]
Monoamine oxidase type B (MAO-B)	TTGP7BY	AOFB_HUMAN	Antagonist	[1]
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Inhibitor	[1], [3]
Synaptic vesicle amine transporter (SLC18A2)	TTNZRI3	VMAT2_HUMAN	Antagonist	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6) Main DME	DECB0K3	CP2D6_HUMAN	Substrate	[4]

Molecular Expression Atlas of This Drug

• The Studied Disease: Discovery agent
• ICD Disease Classification: N.A.

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Synaptic vesicle amine transporter (SLC18A2)	DTT	SLC18A2	2.69E-02	-0.04	-0.11
Monoamine oxidase type B (MAO-B)	DTT	MAOB	2.65E-02	1.12E-02	0.07
Monoamine oxidase type A (MAO-A)	DTT	MAOA	8.14E-01	0.05	0.1
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	7.30E-01	-1.91E-02	-1.41E-01

References

• [1] Differential behavioural and neurochemical effects of para-methoxyamphetamine and 3,4-methylenedioxymethamphetamine in the rat. Prog Neuropsychopharmacol Biol Psychiatry. 2000 Aug;24(6):955-77.
• [2] Naphthylisopropylamine and N-benzylamphetamine derivatives as monoamine oxidase inhibitors. Bioorg Med Chem. 2009 Mar 15;17(6):2452-60.
• [3] Synthesis and serotonin transporter activity of sulphur-substituted alpha-alkyl phenethylamines as a new class of anticancer agents. Eur J Med Chem. 2009 Dec;44(12):4862-88.
• [4] Interactions of amphetamine analogs with human liver CYP2D6. Biochem Pharmacol. 1997 Jun 1;53(11):1605-12.
• [5] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [6] Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
• [7] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [8] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [9] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [10] Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
• [11] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [12] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [13] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [14] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
• [15] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [16] Synthesis and pharmacologic evaluation of 2-endo-amino-3-exo-isopropylbicyclo[2.2.1]heptane: a potent imidazoline1 receptor specific agent. J Med Chem. 1996 Mar 15;39(6):1193-5.
• [17] alpha2A-adrenergic receptors heterosynaptically regulate glutamatergic transmission in the bed nucleus of the stria terminalis. Neuroscience. 2009 Sep 29;163(1):339-51.
• [18] A structure-activity relationship study of benzylic modifications of 4-[1-(1-naphthyl)ethyl]-1H-imidazoles on alpha 1- and alpha 2-adrenergic recep... J Med Chem. 1994 Jul 22;37(15):2328-33.
• [19] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [20] A new arylpiperazine antipsychotic with high D2/D3/5-HT1A/alpha 1A-adrenergic affinity and a low potential for extrapyramidal effects. J Med Chem. 1994 Apr 15;37(8):1060-2.
• [21] Female Sexual Dysfunction: Therapeutic Options and Experimental Challenges. Cardiovasc Hematol Agents Med Chem. 2009 October; 7(4): 260-269.
• [22] Design and synthesis of novel dihydropyridine alpha-1a antagonists. Bioorg Med Chem Lett. 1999 Oct 4;9(19):2843-8.
• [23] Discovery of a new series of centrally active tricyclic isoxazoles combining serotonin (5-HT) reuptake inhibition with alpha2-adrenoceptor blocking... J Med Chem. 2005 Mar 24;48(6):2054-71.
• [24] alpha 2 adrenoceptors: classification, localization, mechanisms, and targets for drugs. J Med Chem. 1982 Dec;25(12):1389-401.
• [25] Augmentation effect of combination therapy of aripiprazole and antidepressants on forced swimming test in mice. Psychopharmacology (Berl). 2009 Sep;206(1):97-107.
• [26] Treatment of comorbid pain with serotonin norepinephrine reuptake inhibitors. CNS Spectr. 2008 Jul;13(7 Suppl 11):22-6.
• [27] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [28] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [29] Psychopharmacological treatment of dermatological patients--when simply talking does not help. J Dtsch Dermatol Ges. 2007 Dec;5(12):1101-6.
• [30] 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.
• [31] Clinically relevant drug interactions with new generation antidepressants and antipsychotics. Ther Umsch. 2009 Jun;66(6):485-92.
• [32] Dopamine signaling is required for depolarization-induced slow current in cerebellar Purkinje cells. J Neurosci. 2009 Jul 1;29(26):8530-8.
• [33] Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
• [34] VMAT2 Inhibitors and the Path to Ingrezza (Valbenazine). Prog Med Chem. 2018;57(1):87-111.
• [35] NBI-98854, a selective monoamine transport inhibitor for the treatment of tardive dyskinesia: A randomized, double-blind, placebo-controlled study. Mov Disord. 2015 Oct;30(12):1681-7.
• [36] Brain imaging of vesicular monoamine transporter type 2 in healthy aging subjects by 18F-FP-(+)-DTBZ PET. PLoS One. 2013 Sep 30;8(9):e75952.
• [37] Design, synthesis and interaction at the vesicular monoamine transporter-2 of lobeline analogs: potential pharmacotherapies for the treatment of psychostimulant abuse. Curr Top Med Chem. 2011;11(9):1103-27.
• [38] The role of combination medical therapy in benign prostatic hyperplasia. Int J Impot Res. 2008 Dec;20 Suppl 3:S33-43.
• [39] Mechanisms of modafinil: A review of current research. Neuropsychiatr Dis Treat. 2007 June; 3(3): 349-364.
• [40] Alfuzosin: a review of the therapeutic use of the prolonged-release formulation given once daily in the management of benign prostatic hyperplasia. Drugs. 2002;62(4):633-53.
• [41] Pharmacokinetics of moxisylyte in healthy volunteers after intracavernous injection of increasing doses. Eur J Clin Pharmacol. 1996;49(5):411-5.
• [42] Induction of prostate apoptosis by alpha1-adrenoceptor antagonists: mechanistic significance of the quinazoline component. Prostate Cancer Prostatic Dis. 2002;5(2):88-95.
• [43] Bunazosin, a selective alpha1-adrenoceptor antagonist, as an anti-glaucoma drug: effects on ocular circulation and retinal neuronal damage. Cardiovasc Drug Rev. 2005 Spring;23(1):43-56.
• [44] The hypotensive effect of trimazosin is not caused solely by alpha 1-adrenoceptor blockade. J Cardiovasc Pharmacol. 1984 Jan-Feb;6(1):142-50.
• [45] Antihypertensive action and blockade of alpha1-adrenoceptors by DL-017, a quinazoline derivative. J Cardiovasc Pharmacol. 2001 Dec;38(6):893-9.
• [46] 5-HT1A receptor ligands and their therapeutic applications: review of new patents.Expert Opin Ther Pat. 2018 Sep;28(9):679-689.
• [47] 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.
• [48] 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.
• [49] 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.
• [50] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [51] 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.
• [52] Rapid detection of Parkinson's disease by SPECT with altropane: a selective ligand for dopamine transporters. Synapse. 1998 Jun;29(2):128-41.
• [53] Anti-obesity drugs. Expert Opin Pharmacother. 2008 Jun;9(8):1339-50.
• [54] 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).
• [55] Emerging drugs for Parkinson's disease. Expert Opin Emerg Drugs. 2006 Sep;11(3):403-17.
• [56] Limitation of adipose tissue enlargement in rats chronically treated with semicarbazide-sensitive amine oxidase and monoamine oxidase inhibitors. Pharmacol Res. 2008 Jun;57(6):426-34.
• [57] Tranylcypromine: new perspectives on an "old" drug. Eur Arch Psychiatry Clin Neurosci. 2006 Aug;256(5):268-73.
• [58] 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: 2490).
• [59] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [60] Glyceraldehyde-3-phosphate dehydrogenase-monoamine oxidase B-mediated cell death-induced by ethanol is prevented by rasagiline and 1-R-aminoindan. Neurotox Res. 2009 Aug;16(2):148-59.
• [61] Novel monoamine oxidase inhibitors, 3-(2-aminoethoxy)-1,2-benzisoxazole derivatives, and their differential reversibility. Jpn J Pharmacol. 2002 Feb;88(2):174-82.
• [62] Dose-dependent activation of distinct hypertrophic pathways by serotonin in cardiac cells. Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H821-8.
• [63] Multiple mechanisms of action: the pharmacological profile of budipine. J Neural Transm Suppl. 1999;56:83-105.
• [64] Efficacy of citalopram and moclobemide in patients with social phobia: some preliminary findings. Hum Psychopharmacol. 2002 Dec;17(8):401-5.
• [65] Tramadol and another atypical opioid meperidine have exaggerated serotonin syndrome behavioural effects, but decreased analgesic effects, in genetically deficient serotonin transporter (SERT) mice. Int J Neuropsychopharmacol. 2009 Mar 11:1-11.
• [66] Further investigation into the mechanism of tachykinin NK(2) receptor-triggered serotonin release from guinea-pig proximal colon. J Pharmacol Sci. 2009 May;110(1):122-6.
• [67] MAOIs in the contemporary treatment of depression. Neuropsychopharmacology. 1995 May;12(3):185-219.
• [68] Binding of beta-carbolines at imidazoline I2 receptors: a structure-affinity investigation. Bioorg Med Chem Lett. 2004 Feb 23;14(4):999-1002.
• [69] Inhibition of rat brain monoamine oxidase activities by psoralen and isopsoralen: implications for the treatment of affective disorders. Pharmacol Toxicol. 2001 Feb;88(2):75-80.
• [70] Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
• [71] Ladostigil: a novel multimodal neuroprotective drug with cholinesterase and brain-selective monoamine oxidase inhibitory activities for Alzheimer's disease treatment. Curr Drug Targets. 2012 Apr;13(4):483-94.
• [72] Reversible inhibitors of monoamine oxidase-A (RIMAs): robust, reversible inhibition of human brain MAO-A by CX157. Neuropsychopharmacology. 2010 Feb;35(3):623-31.
• [73] Proposed structural basis of interaction of piperine and related compounds with monoamine oxidases. Bioorg Med Chem Lett. 2010 Jan 15;20(2):537-40.
• [74] Pharmacophore identification of alpha(1A)-adrenoceptor antagonists. Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.
• [75] Pharma & Vaccines. Product Development Pipeline. April 29 2009.
• [76] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [77] Alpha-Adrenergic activity and cardiovascular effects of besipirdine HCl (HP 749) and metabolite P7480 in vitro and in the conscious rat and dog. J Pharmacol Exp Ther. 1997 Apr;281(1):337-46.
• [78] 3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents. J Med Chem. 1996 Jan 5;39(1):143-8.