Details of the Drug

General Information of Drug (ID: DMWIX23)

• Drug Name: Metaraminol
• Synonyms: Araminol; Hydroxynorephedrine; Isophenylephrine; Metaradrin; Metaradrine; Metaraminolum; Pressonex; Pressorol; Icoral B; Metaraminolum [Latin]; Aramine (TN); L-Metaraminol; M-Hydroxy norephedrine; M-Hydroxynorephedrine; M-Hydroxyphenylpropanolamine; M-Hydroxypropadrine; Meta-Hydroxynorephedrine; Metaraminol (INN); Metaraminol [INN:BAN]; Metaraminolum [INN-Latin]; Alpha-(1-Aminoethyl)-3-hydroxybenzenemethanol; Alpha-(1-Aminoethyl)-m-hydroxybenzyl alcohol; Alpha-(m-Hydroxyphenyl)-beta-aminopropanol; M-Hydroxy-alpha-(1-aminoethyl)-benzyl alcohol; Benzenemethanol, alpha-(1-aminoethyl)-3-hydroxy-, (R-(R*,S*))-(9CI); (-)-Erythro-metaraminol; 1-(m-Hydroxyphenyl)-2-amino-1-propanol; 1-Metaraminol; 1-alpha-(1-Aminoethyl)-m-hydroxybenzyl alcohol; 2-Amino-1-(m-hydroxyphenyl)-1-propanol; 3-Hydroxyphenylisopropanolamine; 3-[(1R,2S)-2-amino-1-hydroxypropyl]phenol

Indication

Disease Entry	ICD 11	Status	REF
Hypotension	BA20-BA21	Approved	[1]

• Therapeutic Class: Antihypertensive Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 167.2
  Logarithm of the Partition Coefficient (xlogp); -0.4
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 3
• ADMET Property:
  Metabolism: The drug is metabolized via the hepatic []
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 49.81776 micromolar/kg/day [2]
• Chemical Identifiers:
  Formula: C9H13NO2
  IUPAC Name: 3-[(1R,2S)-2-amino-1-hydroxypropyl]phenol
  Canonical SMILES: C[C@@H]([C@@H](C1=CC(=CC=C1)O)O)N
  InChI: InChI=1S/C9H13NO2/c1-6(10)9(12)7-3-2-4-8(11)5-7/h2-6,9,11-12H,10H2,1H3/t6-,9-/m0/s1
  InChIKey: WXFIGDLSSYIKKV-RCOVLWMOSA-N
• Cross-matching ID:
  PubChem CID: 5906
  ChEBI ID: CHEBI:6794
  CAS Number: 54-49-9
  DrugBank ID: DB00610
  TTD ID: D04EYC
  VARIDT ID: DR01169

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Agonist	[3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Hypotension
• ICD Disease Classification: BA20-BA21

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Dopamine D2 receptor (D2R)	DTT	DRD2	2.50E-02	-0.08	-0.49

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Metaraminol (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Methylene blue	DMJAPE7	Major	Additive hypertensive effects by the combination of Metaraminol and Methylene blue.	Acquired methaemoglobinaemia [3A93]	[4]
Droxidopa	DM5YF4M	Moderate	Additive hypertensive effects by the combination of Metaraminol and Droxidopa.	Autonomic nervous system disorder [8D87]	[5]
Levomilnacipran	DMV26S8	Moderate	Increased risk of rapid heart rate by the combination of Metaraminol and Levomilnacipran.	Chronic pain [MG30]	[6]
Selegiline	DM6034S	Major	Increased risk of hyperpyrexia by the combination of Metaraminol and Selegiline.	Depression [6A70-6A7Z]	[4]
Isocarboxazid	DMAF1NB	Major	Increased risk of hyperpyrexia by the combination of Metaraminol and Isocarboxazid.	Depression [6A70-6A7Z]	[4]
Milnacipran	DMBFE74	Moderate	Increased risk of rapid heart rate by the combination of Metaraminol and Milnacipran.	Depression [6A70-6A7Z]	[6]
Tranylcypromine	DMGB5RE	Major	Increased risk of hyperpyrexia by the combination of Metaraminol and Tranylcypromine.	Depression [6A70-6A7Z]	[7]
Desvenlafaxine	DMHD4PE	Moderate	Increased risk of rapid heart rate by the combination of Metaraminol and Desvenlafaxine.	Depression [6A70-6A7Z]	[6]
Phenelzine	DMHIDUE	Major	Additive hypertensive effects by the combination of Metaraminol and Phenelzine.	Depression [6A70-6A7Z]	[4]
Ergotamine	DMKR3C5	Major	Additive hypertensive effects by the combination of Metaraminol and Ergotamine.	Headache [8A80-8A84]	[8]
Procarbazine	DMIK367	Major	Increased risk of hyperpyrexia by the combination of Metaraminol and Procarbazine.	Hodgkin lymphoma [2B30]	[4]
Ozanimod	DMT6AM2	Moderate	Increased risk of hyperpyrexia by the combination of Metaraminol and Ozanimod.	Multiple sclerosis [8A40]	[4]
Sibutramine	DMFJTDI	Moderate	Additive hypertensive effects by the combination of Metaraminol and Sibutramine.	Obesity [5B80-5B81]	[9]
Safinamide	DM0YWJC	Moderate	Decreased metabolism of Metaraminol caused by Safinamide mediated inhibition of non-CYP450 enzyme.	Parkinsonism [8A00]	[10]
Rasagiline	DM3WKQ4	Moderate	Additive hypertensive effects by the combination of Metaraminol and Rasagiline.	Parkinsonism [8A00]	[4]

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: 7229).
• [2] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [3] Alpha1-adrenoceptor stimulation enhances experimental gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. Int J Cancer. 1998 Jul 29;77(3):467-9.
• [4] Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6. [PMID: 1116424]
• [5] Product Information. Northera (droxidopa). Chelsea Therapeutics Inc, Charlotte, NC.
• [6] Product Information. Cymbalta (duloxetine). Lilly, Eli and Company, Indianapolis, IN.
• [7] Davies B, Bannister R, Sever P "Pressor amines and monoamine-oxidase inhibitors for treatment of postural hypotension in autonomic failure: limitations and hazards." Lancet 1 (1978): 172-5. [PMID: 74603]
• [8] Barthel W, Glusa E, Koth W "Interactions of dihydroergotamine with etilefrine in human leg veins in vitro and in situ." Int J Clin Pharmacol Ther Toxicol 25 (1987): 63-9. [PMID: 2881898]
• [9] Mendelson J, Jones RT, Upton R, Jacob P 3rd "Methamphetamine and ethanol interactions in humans." Clin Pharmacol Ther 57 (1995): 559-68. [PMID: 7768079]
• [10] Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".