Details of the Drug

General Information of Drug (ID: DMNMW9R)

• Drug Name: Pramipexole
• Synonyms: Mirapex; Pramipexol; Pramipexolum; SUD919CL2Y; Mirapex (TN); Mirapexin (TN); Pramipexole [USAN:INN]; SND-919; Sifrol(TN); U-98528E; Pramipexole (USAN/INN); (-)-Pramipexole; (6S)-6-N-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine; (6S)-N(6)-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine; (6S)-N6-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine; (S)-2-Amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole; 111GE001; 2-amino-4,5,6,7-tetrahydro-6-propylaminobenzothiazole; 2-amino-6-propylaminotetrahydrobenzothiazole

Indication

Disease Entry	ICD 11	Status	REF
Parkinson disease	8A00.0	Approved	[1]

• Therapeutic Class: Antiparkinson Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 211.33
  Logarithm of the Partition Coefficient (xlogp); 1.9
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [2]
  Bioavailability: The bioavailability of drug is 90% []
  Clearance: The renal clearance of drug is 400 mL/min []
  Elimination: 90% of a pramipexole dose is found in the urine (almost entirely as unchanged drug) []
  Half-life: The concentration or amount of drug in body reduced by one-half in 8.5 - 12 hours []
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.3042 micromolar/kg/day [3]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.85% [4]
  Vd: The volume of distribution (Vd) of drug is 500 L []
  Water Solubility: The ability of drug to dissolve in water is measured as 0.2 mg/mL [2]
• Chemical Identifiers:
  Formula: C10H17N3S
  IUPAC Name: (6S)-6-N-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine
  Canonical SMILES: CCCN[C@H]1CCC2=C(C1)SC(=N2)N
  InChI: InChI=1S/C10H17N3S/c1-2-5-12-7-3-4-8-9(6-7)14-10(11)13-8/h7,12H,2-6H2,1H3,(H2,11,13)/t7-/m0/s1
  InChIKey: FASDKYOPVNHBLU-ZETCQYMHSA-N
• Cross-matching ID:
  PubChem CID: 119570
  ChEBI ID: CHEBI:8356
  CAS Number: 104632-26-0
  DrugBank ID: DB00413
  TTD ID: D0G8NN
  VARIDT ID: DR00620
  ACDINA ID: D00546
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

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	Modulator	[5]
Dopamine D3 receptor (D3R)	TT4C8EA	DRD3_HUMAN	Modulator	[5]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[6]
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[7]

Molecular Expression Atlas of This Drug

• The Studied Disease: Parkinson disease
• ICD Disease Classification: 8A00.0

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
Organic cation transporter 1 (SLC22A1)	DTP	SLC22A1	8.54E-01	1.24E-02	7.20E-02
Organic cation transporter 2 (SLC22A2)	DTP	SLC22A2	8.22E-01	-1.05E-02	-3.83E-02

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Pramipexole

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Levodopa	DMN3E57	Moderate	Additive dopaminergic effects by the combination of Pramipexole and Levodopa.	Parkinsonism [8A00]	[8]

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Memantine	DMD9WSC	Minor	Additive dopaminergic effects by the combination of Pramipexole and Memantine.	Alzheimer disease [8A20]	[9]
Promazine	DMZAL7W	Moderate	Antagonize the effect of Pramipexole when combined with Promazine.	Appearance/behaviour symptom [MB23]	[10]
Olopatadine	DMKMWQG	Moderate	Additive CNS depression effects by the combination of Pramipexole and Olopatadine.	Conjunctiva disorder [9A60]	[11]
Ethanol	DMDRQZU	Moderate	Additive CNS depression effects by the combination of Pramipexole and Ethanol.	Cystitis [GC00]	[11]
OPC-34712	DMHG57U	Moderate	Antagonize the effect of Pramipexole when combined with OPC-34712.	Depression [6A70-6A7Z]	[10]
Amoxapine	DMKITQE	Moderate	Additive CNS depression effects by the combination of Pramipexole and Amoxapine.	Depression [6A70-6A7Z]	[10]
Esketamine	DMVU687	Moderate	Additive CNS depression effects by the combination of Pramipexole and Esketamine.	Depression [6A70-6A7Z]	[12]
Brimonidine	DMQLT4N	Moderate	Additive CNS depression effects by the combination of Pramipexole and Brimonidine.	Glaucoma [9C61]	[13]
Propiomazine	DMKY8V1	Moderate	Additive CNS depression effects by the combination of Pramipexole and Propiomazine.	Insomnia [7A00-7A0Z]	[10]
ITI-007	DMUQ1DO	Moderate	Additive hypotensive effects by the combination of Pramipexole and ITI-007.	Insomnia [7A00-7A0Z]	[10]
Allopregnanolone	DMNLHAC	Moderate	Additive CNS depression effects by the combination of Pramipexole and Allopregnanolone.	Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z]	[14]
Flibanserin	DM70DTN	Moderate	Additive CNS depression effects by the combination of Pramipexole and Flibanserin.	Mood disorder [6A60-6E23]	[15]
Thalidomide	DM70BU5	Moderate	Additive CNS depression effects by the combination of Pramipexole and Thalidomide.	Multiple myeloma [2A83]	[16]
Prochlorperazine	DM53SRA	Moderate	Additive CNS depression effects by the combination of Pramipexole and Prochlorperazine.	Nausea/vomiting [MD90]	[10]
Promethazine	DM6I5GR	Moderate	Antagonize the effect of Pramipexole when combined with Promethazine.	Nausea/vomiting [MD90]	[10]
Metoclopramide	DMFA5MY	Moderate	Additive CNS depression effects by the combination of Pramipexole and Metoclopramide.	Nausea/vomiting [MD90]	[10]
Apraclonidine	DMO4PVE	Moderate	Additive CNS depression effects by the combination of Pramipexole and Apraclonidine.	Optic nerve disorder [9C40]	[13]
Dextropropoxyphene	DM23HCX	Major	Decreased metabolism of Pramipexole caused by Dextropropoxyphene mediated inhibition of CYP450 enzyme.	Pain [MG30-MG3Z]	[17]
Levomepromazine	DMIKFEL	Moderate	Antagonize the effect of Pramipexole when combined with Levomepromazine.	Psychotic disorder [6A20-6A25]	[10]
Fluphenazine	DMIT8LX	Moderate	Antagonize the effect of Pramipexole when combined with Fluphenazine.	Psychotic disorder [6A20-6A25]	[10]
Quetiapine	DM1N62C	Moderate	Antagonize the effect of Pramipexole when combined with Quetiapine.	Schizophrenia [6A20]	[10]
Mesoridazine	DM2ZGAN	Moderate	Antagonize the effect of Pramipexole when combined with Mesoridazine.	Schizophrenia [6A20]	[10]
Thioridazine	DM35M8J	Moderate	Antagonize the effect of Pramipexole when combined with Thioridazine.	Schizophrenia [6A20]	[10]
Aripiprazole	DM3NUMH	Moderate	Additive CNS depression effects by the combination of Pramipexole and Aripiprazole.	Schizophrenia [6A20]	[10]
Iloperidone	DM6AUFY	Moderate	Antagonize the effect of Pramipexole when combined with Iloperidone.	Schizophrenia [6A20]	[10]
Paliperidone	DM7NPJS	Moderate	Antagonize the effect of Pramipexole when combined with Paliperidone.	Schizophrenia [6A20]	[10]
Haloperidol	DM96SE0	Moderate	Antagonize the effect of Pramipexole when combined with Haloperidol.	Schizophrenia [6A20]	[10]
Perphenazine	DMA4MRX	Moderate	Antagonize the effect of Pramipexole when combined with Perphenazine.	Schizophrenia [6A20]	[10]
Molindone	DMAH70G	Moderate	Antagonize the effect of Pramipexole when combined with Molindone.	Schizophrenia [6A20]	[10]
Chlorpromazine	DMBGZI3	Moderate	Antagonize the effect of Pramipexole when combined with Chlorpromazine.	Schizophrenia [6A20]	[10]
Thiothixene	DMDINC4	Moderate	Antagonize the effect of Pramipexole when combined with Thiothixene.	Schizophrenia [6A20]	[10]
Trifluoperazine	DMKBYWI	Moderate	Antagonize the effect of Pramipexole when combined with Trifluoperazine.	Schizophrenia [6A20]	[10]
Risperidone	DMN6DXL	Moderate	Additive hypotensive effects by the combination of Pramipexole and Risperidone.	Schizophrenia [6A20]	[10]
Amisulpride	DMSJVAM	Major	Antagonize the effect of Pramipexole when combined with Amisulpride.	Schizophrenia [6A20]	[12]
Asenapine	DMSQZE2	Moderate	Antagonize the effect of Pramipexole when combined with Asenapine.	Schizophrenia [6A20]	[10]
Pimozide	DMW83TP	Moderate	Antagonize the effect of Pramipexole when combined with Pimozide.	Schizophrenia [6A20]	[10]
Tizanidine	DMR2IQ4	Moderate	Additive CNS depression effects by the combination of Pramipexole and Tizanidine.	Tonus and reflex abnormality [MB47]	[18]
Methdilazine	DMAUHQX	Moderate	Antagonize the effect of Pramipexole when combined with Methdilazine.	Vasomotor/allergic rhinitis [CA08]	[10]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
D&C red no. 27	E00381	83511	Colorant
FD&C blue no. 1	E00263	19700	Colorant
FD&C blue no. 2	E00446	2723854	Colorant
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Quinoline yellow WS	E00309	24671	Colorant
Sodium citrate anhydrous	E00102	6224	Alkalizing agent; Buffering agent; Complexing agent; Emulsifying agent
Sodium stearyl fumarate	E00545	23665634	lubricant
Sunset yellow FCF	E00255	17730	Colorant
Crospovidone	E00626	Not Available	Disintegrant
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Magnesium stearate	E00208	11177	lubricant
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Soybean lecithin	E00637	Not Available	Other agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Vinylpyrrolidone	E00668	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Water	E00035	962	Solvent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Pramipexole 0.5 mg tablet	0.5 mg	Oral Tablet	Oral
Pramipexole 0.75 mg tablet	0.75 mg	Oral Tablet	Oral
Pramipexole 1 mg tablet	1 mg	Oral Tablet	Oral
Pramipexole 1.5 mg tablet	1.5 mg	Oral Tablet	Oral
Pramipexole 0.125 mg tablet	0.125 mg	Oral Tablet	Oral
Pramipexole 0.25 mg tablet	0.25 mg	Oral Tablet	Oral
Pramipexole 0.375 mg tablet	0.375 mg	24 HR Extended Release Oral Tablet	Oral
Pramipexole 0.75 mg tablet	0.75 mg	24 HR Extended Release Oral Tablet	Oral
Pramipexole 1.5 mg tablet	1.5 mg	24 HR Extended Release Oral Tablet	Oral
Pramipexole 2.25 mg tablet	2.25 mg	24 HR Extended Release Oral Tablet	Oral
Pramipexole 3 mg tablet	3 mg	24 HR Extended Release Oral Tablet	Oral
Pramipexole 3.75 mg tablet	3.75 mg	24 HR Extended Release Oral Tablet	Oral
Pramipexole 4.5 mg tablet	4.5 mg	24 HR Extended Release Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

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: 953).
• [2] BDDCS applied to over 900 drugs
• [3] 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
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] OCT1 polymorphism is associated with response and survival time in anti-Parkinsonian drug users. Neurogenetics. 2011 Feb;12(1):79-82.
• [7] Uptake of pramipexole by human organic cation transporters. Mol Pharm. 2010 Aug 2;7(4):1342-7.
• [8] Kompoliti K, Adler CH, Raman R, et al. "Gender and pramipexole effects on levodopa pharmacokinetics and pharmacodynamics." Neurology 58 (2002): 1418-22. [PMID: 12011296]
• [9] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [10] Mims RB, Scott CL, Modebe O, Bethune JE "Inhibition of L-dopa-induced growth hormone stimulation by pyridoxine and chlorpromazine." J Clin Endocrinol Metab 40 (1975): 256-9. [PMID: 1117978]
• [11] Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7. [PMID: 3725002]
• [12] Cerner Multum, Inc. "Australian Product Information.".
• [13] Product Information. Alphagan (brimonidine ophthalmic). Allergan Inc, Irvine, CA.
• [14] Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
• [15] Product Information. Addyi (flibanserin). Sprout Pharmaceuticals, Raleigh, NC.
• [16] Product Information. Thalomid (thalidomide). Celgene Corporation, Warren, NJ.
• [17] Hansen BS, Dam M, Brandt J, et al "Influence of dextropropoxyphene on steady state serum levels and protein binding of three anti-epileptic drugs in man." Acta Neurol Scand 61 (1980): 357-67. [PMID: 6998251]
• [18] Product Information. Zanaflex (tizanidine). Acorda Therapeutics, Hawthorne, NY.