Identification

Name
Milnacipran
Accession Number
DB04896
Type
Small Molecule
Groups
Approved, Investigational
Description

Milnacipran is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class. It more potently inhibits norepinephrine uptake than serotonin. It is provided as a racemic mixture. FDA approved in January 2009.

Structure
Thumb
Synonyms
  • (-)-milnacipran
  • Midalcipran
  • Milnacipran
  • Milnacipranum
External IDs
F2207
Product Ingredients
IngredientUNIICASInChI Key
Milnacipran HydrochlorideRNZ43O5WW5101152-94-7XNCDYJFPRPDERF-PBCQUBLHSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SavellaTablet, film coated50 mg/1OralStat Rx USA2009-04-17Not applicableUs
SavellaTablet, film coated25 mg/1OralRebel Distributors2009-04-17Not applicableUs
SavellaTablet, film coated50 mg/1OralAllergan2009-04-17Not applicableUs0456 155020180913 8702 1gh427g
SavellaTablet, film coated12.5 mg/1OralAllergan2009-04-17Not applicableUs00456 1512 60 nlmimage10 313f1888
SavellaTablet, film coated25 mg/1OralUnit Dose Services2009-04-17Not applicableUs50436 999320180913 8702 10yh6em
SavellaTablet, film coated50 mg/1OralLake Erie Medical &Surgical Supply Dba Quality Care Products Llc2011-11-17Not applicableUs
SavellaTablet, film coated25 mg/1OralStat Rx USA2009-04-17Not applicableUs
SavellaTablet, film coated25 mg/1OralLake Erie Medical Dba Quality Care Produts Llc2009-04-172016-12-31Us
SavellaTablet, film coated100 mg/1OralPhysicians Total Care, Inc.2010-01-19Not applicableUs54868 602420180907 15195 73eoac
SavellaTablet, film coated100 mg/1OralStat Rx USA2009-04-17Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Milnacipran HClTablet100 mg/1OralAmneal Pharmaceuticals2014-01-31Not applicableUs
Milnacipran HClTablet12.5 mg/1OralAmneal Pharmaceuticals2014-01-31Not applicableUs
Milnacipran HClTablet50 mg/1OralAmneal Pharmaceuticals2014-01-31Not applicableUs
Milnacipran HClTablet25 mg/1OralAmneal Pharmaceuticals2014-01-31Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
SavellaMilnacipran Hydrochloride (12.5 mg/1) + Milnacipran Hydrochloride (25 mg/1) + Milnacipran Hydrochloride (50 mg/1)KitOralAllergan2009-04-17Not applicableUs
SavellaMilnacipran Hydrochloride (12.5 mg/1) + Milnacipran Hydrochloride (25 mg/1) + Milnacipran Hydrochloride (50 mg/1)KitOralAllergan2009-04-17Not applicableUs
SavellaMilnacipran Hydrochloride (12.5 mg/1) + Milnacipran Hydrochloride (25 mg/1) + Milnacipran Hydrochloride (50 mg/1)KitOralAllergan2009-04-17Not applicableUs
International/Other Brands
Dalcipran / Ixel / Toledomin
Categories
UNII
ES1O38J3C4
CAS number
92623-85-3
Weight
Average: 246.348
Monoisotopic: 246.173213336
Chemical Formula
C15H22N2O
InChI Key
GJJFMKBJSRMPLA-HIFRSBDPSA-N
InChI
InChI=1S/C15H22N2O/c1-3-17(4-2)14(18)15(10-13(15)11-16)12-8-6-5-7-9-12/h5-9,13H,3-4,10-11,16H2,1-2H3/t13-,15+/m1/s1
IUPAC Name
(1R,2S)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropane-1-carboxamide
SMILES
CCN(CC)C(=O)[C@@]1(C[C@@H]1CN)C1=CC=CC=C1

Pharmacology

Indication

Milnacipran is used to treat moderate to severe clinical depression but this indication is not yet FDA-approved in the USA. Milnacipran is labelled for the treatment of fibromyalgia pain.

Associated Conditions
Pharmacodynamics

Although milnacipran prolongs the QTc interval, the increase is not considered clinically significant.

Mechanism of action

Milnacipran inhibits norepinephrine and serotonin reuptake in a 3:1 ratio, in practical use this means a balanced (equal) action upon both transmitters. The serotonin reuptake inhibition is likely to improve depression, while the norepinephrine reuptake inihibition probably improves chronic pain. Milnacipran exerts no significant actions on postynaptic H1, alpha-1, D1, D2, and muscarinic receptors, as well as on benzodiazepine/opiate binding sites. [Wikipedia]

TargetActionsOrganism
ASodium-dependent serotonin transporter
inhibitor
Human
ASodium-dependent noradrenaline transporter
inhibitor
Human
UNMDA receptor
inhibitor
Human
Absorption

Milnacipran is well absorbed following oral administration with an absolute bioavailability of 85-90%. Meals have no effect on absorption. Peak concentrations occur 2 -4 hours post-administration and is delayed in elderly patients. Time to steady state = 36 - 48 hours;

Volume of distribution

400 L, following a single IV dose to a healthy subject.

Protein binding

Plasma protein binding is 13%.

Metabolism

Hepatic metabolism of milnacipran occurs via glucuronidation. No involvement of CYP450 isozymes or active metabolites found.

Route of elimination

It is excreted predominantly unchanged in urine (50%- 60%, 24% as l-milnacipran and 31% as d-milnacipran). The l-milnacipran carbamoyl-O-glucuronide was the major metabolite excreted in urine and accounted for approximately 17% of the dose; approximately 2% of the dose was excreted in urine as d-milnacipran carbamoyl-O-glucuronide. Approximately 8% of the dose was excreted in urine as the N-desethyl milnacipran metabolite.

Half life

The terminal elimination half-life, when given to healthy subjects is 6-8 hours. When given to severe renal impairment patients is 7 - 10 hours. The active enantiomer, d-milnacipran, has a longer elimination half-life (8-10 hours) than the l-enantiomer (4-6 hours).

Clearance
Not Available
Toxicity

LD50, oral, rat: 213 mg/kg. The most frequently occurring adverse reactions (≥ 5% and greater than placebo) were nausea, headache, constipation, dizziness, insomnia, hot flush, hyperhidrosis, vomiting, palpitations, heart rate increased, dry mouth, and hypertension.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
4-MethoxyamphetamineMilnacipran may increase the tachycardic activities of 4-Methoxyamphetamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Milnacipran.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the serotonergic activities of Milnacipran.
AbciximabMilnacipran may increase the antiplatelet activities of Abciximab.
AcarboseMilnacipran may increase the hypoglycemic activities of Acarbose.
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Milnacipran.
AceclofenacMilnacipran may increase the antiplatelet activities of Aceclofenac.
AcenocoumarolThe risk or severity of adverse effects can be increased when Milnacipran is combined with Acenocoumarol.
AcepromazineThe risk or severity of adverse effects can be increased when Acepromazine is combined with Milnacipran.
AceprometazineThe risk or severity of adverse effects can be increased when Aceprometazine is combined with Milnacipran.
Food Interactions
Not Available

References

Synthesis Reference

Jean Deregnaucourt, "Use of the (1S,2R) enantiomer of milnacipran for the preparation of a drug." U.S. Patent US20040259953, issued December 23, 2004.

US20040259953
General References
  1. Leo RJ, Brooks VL: Clinical potential of milnacipran, a serotonin and norepinephrine reuptake inhibitor, in pain. Curr Opin Investig Drugs. 2006 Jul;7(7):637-42. [PubMed:16869117]
  2. Sato S, Yamakawa Y, Terashima Y, Ohta H, Asada T: Efficacy of milnacipran on cognitive dysfunction with post-stroke depression: preliminary open-label study. Psychiatry Clin Neurosci. 2006 Oct;60(5):584-9. [PubMed:16958942]
  3. Simon LS: Is milnacipran effective in treating pain in patients with fibromyalgia? Nat Clin Pract Rheumatol. 2006 Mar;2(3):126-7. [PubMed:16932669]
  4. Soya A, Terao T, Nakajima M, Kojima H, Okamoto T, Inoue Y, Iwakawa M, Shinkai K, Yoshimura R, Ueta Y, Nakamura J: Effects of repeated milnacipran administration on brain serotonergic and noradrenergic functions in healthy volunteers. Psychopharmacology (Berl). 2006 Sep;187(4):526-7. Epub 2006 Jul 8. [PubMed:16830129]
  5. King T, Rao S, Vanderah T, Chen Q, Vardanyan A, Porreca F: Differential blockade of nerve injury-induced shift in weight bearing and thermal and tactile hypersensitivity by milnacipran. J Pain. 2006 Jul;7(7):513-20. [PubMed:16814690]
  6. Moojen VK, Martins MR, Reinke A, Feier G, Agostinho FR, Cechin EM, Quevedo J: Effects of milnacipran in animal models of anxiety and memory. Neurochem Res. 2006 Apr;31(4):571-7. Epub 2006 May 9. [PubMed:16758367]
  7. Moret C, Charveron M, Finberg JP, Couzinier JP, Briley M: Biochemical profile of midalcipran (F 2207), 1-phenyl-1-diethyl-aminocarbonyl-2-aminomethyl-cyclopropane (Z) hydrochloride, a potential fourth generation antidepressant drug. Neuropharmacology. 1985 Dec;24(12):1211-9. [PubMed:3005901]
  8. Briley M, Prost JF, Moret C: Preclinical pharmacology of milnacipran. Int Clin Psychopharmacol. 1996 Sep;11 Suppl 4:9-14. [PubMed:8923122]
  9. Puozzo C, Panconi E, Deprez D: Pharmacology and pharmacokinetics of milnacipran. Int Clin Psychopharmacol. 2002 Jun;17 Suppl 1:S25-35. [PubMed:12369608]
  10. Leinonen E, Lepola U, Koponen H, Mehtonen OP, Rimon R: Long-term efficacy and safety of milnacipran compared to clomipramine in patients with major depression. Acta Psychiatr Scand. 1997 Dec;96(6):497-504. [PubMed:9421348]
  11. Papakostas GI, Fava M: A meta-analysis of clinical trials comparing milnacipran, a serotonin--norepinephrine reuptake inhibitor, with a selective serotonin reuptake inhibitor for the treatment of major depressive disorder. Eur Neuropsychopharmacol. 2007 Jan;17(1):32-6. Epub 2006 Jun 8. [PubMed:16762534]
  12. Kako Y, Niwa Y, Toyomaki A, Yamanaka H, Kitagawa N, Denda K, Koyama T: A case of adult attention-deficit/hyperactivity disorder alleviated by milnacipran. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Apr 13;31(3):772-5. Epub 2007 Jan 12. [PubMed:17300859]
  13. Bernstein CD, Albrecht KL, Marcus DA: Milnacipran for fibromyalgia: a useful addition to the treatment armamentarium. Expert Opin Pharmacother. 2013 May;14(7):905-16. doi: 10.1517/14656566.2013.779670. Epub 2013 Mar 19. [PubMed:23506481]
External Links
Human Metabolome Database
HMDB0015602
KEGG Drug
D08222
PubChem Compound
65833
PubChem Substance
46506141
ChemSpider
59245
BindingDB
86420
ChEBI
94468
ChEMBL
CHEMBL252923
Therapeutic Targets Database
DAP001155
PharmGKB
PA164752812
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Milnacipran
ATC Codes
N06AX17 — Milnacipran
FDA label
Download (332 KB)
MSDS
Download (83.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceFibromyalgia1
2CompletedTreatmentFibromyalgia Syndrome1
2CompletedTreatmentLow Back Pain (LBP)1
2RecruitingTreatmentPain, Neuropathic1
2TerminatedTreatmentFibromyalgia Syndrome, Primary1
2TerminatedTreatmentFibromyalgia, Primary1
2TerminatedTreatmentIrritable Bowel Syndrome (IBS)1
2Unknown StatusTreatmentFibromylagia1
2, 3CompletedTreatmentFibromyalgia1
2, 3RecruitingTreatmentDepression1
3CompletedTreatmentDepression1
3CompletedTreatmentFibromyalgia3
3CompletedTreatmentFibromyalgia Syndrome2
3CompletedTreatmentFibromyalgia / Neurocognition1
3CompletedTreatmentVestibulodynia / Vulvodynia1
3TerminatedTreatmentFibromyalgia2
3WithdrawnTreatmentBack Pain1
4CompletedBasic ScienceFibromyalgia1
4CompletedTreatmentAsperger's Syndrome / Aspergers Syndrome / Autism Spectrum Conditions/Disorders1
4CompletedTreatmentDegenerative Joint Disease / Knee Osteoarthritis (Knee OA) / Pain, Chronic1
4CompletedTreatmentFibromyalgia3
4CompletedTreatmentFibromyalgia / Sleep / Sleep disorders and disturbances1
4CompletedTreatmentKnee Pain After Total Knee Arthroplasty / Osteoarthritis Pain1
4CompletedTreatmentRadicular Pain Related to Lumbosacral Disc Disease1
4CompletedTreatmentRheumatoid Arthritis2
4CompletedTreatmentShoulder Pain Chronic1
4Unknown StatusPreventionChronic Migraine / Migraine With Aura / Migraine Without Aura1
4Unknown StatusTreatmentFibromyalgia1
4Unknown StatusTreatmentOsteoarthritis (OA)1
4WithdrawnTreatmentFibromyalgia / Systemic Lupus Erythematosus (SLE) / Widespread Pain1
Not AvailableActive Not RecruitingTreatmentDepression2
Not AvailableCompletedPreventionChronic Migraine1
Not AvailableRecruitingTreatmentAdverse Reaction to Drug / Depression1
Not AvailableRecruitingTreatmentDepression / Depressive Symptoms1
Not AvailableRecruitingTreatmentPain, Chronic / Post Treatment Lyme Syndrome (PTLS)1
Not AvailableTerminatedTreatmentIdiopathic Peripheral Neuropathy1
Not AvailableUnknown StatusPreventionDepression / Stroke, Ischemic1
Not AvailableUnknown StatusTreatmentMajor Depressive Disorder (MDD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Forest Laboratories Inc.
  • Forest Pharmaceuticals
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
TabletOral100 mg/1
TabletOral12.5 mg/1
TabletOral25 mg/1
TabletOral50 mg/1
KitOral
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral12.5 mg/1
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral50 mg/1
Prices
Unit descriptionCostUnit
Savella 100 mg tablet2.13USD tablet
Savella 12.5 mg tablet2.13USD tablet
Savella 25 mg tablet2.13USD tablet
Savella 50 mg tablet2.13USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6602911No2003-01-142023-01-14Us
US6992110No2001-11-052021-11-05Us
US7888342No2001-11-052021-11-05Us
US7994220No2009-09-192029-09-19Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)179°C Bernstein CD, Albrecht KL, Marcus DA: Milnacipran for fibromyalgia: a useful addition to the treatment armamentarium. Expert Opin Pharmacother. 2013 Mar 19. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/23506481
water solubility19 mg/mLMSDS
Predicted Properties
PropertyValueSource
Water Solubility1.23 mg/mLALOGPS
logP1.72ALOGPS
logP1.42ChemAxon
logS-2.3ALOGPS
pKa (Strongest Basic)9.83ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area46.33 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity73.81 m3·mol-1ChemAxon
Polarizability28.03 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9889
Caco-2 permeable+0.5914
P-glycoprotein substrateSubstrate0.5928
P-glycoprotein inhibitor INon-inhibitor0.902
P-glycoprotein inhibitor IINon-inhibitor0.8787
Renal organic cation transporterNon-inhibitor0.8119
CYP450 2C9 substrateNon-substrate0.8494
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6514
CYP450 1A2 substrateNon-inhibitor0.6383
CYP450 2C9 inhibitorNon-inhibitor0.7697
CYP450 2D6 inhibitorNon-inhibitor0.7718
CYP450 2C19 inhibitorNon-inhibitor0.8587
CYP450 3A4 inhibitorNon-inhibitor0.6327
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7004
Ames testNon AMES toxic0.8013
CarcinogenicityNon-carcinogens0.5456
BiodegradationNot ready biodegradable0.9972
Rat acute toxicity2.6162 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.993
hERG inhibition (predictor II)Non-inhibitor0.6823
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001i-1590000000-14ea613049f0be797cc6

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylacetamides. These are amide derivatives of phenylacetic acids.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenylacetamides
Direct Parent
Phenylacetamides
Alternative Parents
Aralkylamines / Cyclopropanecarboxylic acids and derivatives / Tertiary carboxylic acid amides / Amino acids and derivatives / Organopnictogen compounds / Organic oxides / Monoalkylamines / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Phenylacetamide / Aralkylamine / Cyclopropanecarboxylic acid or derivatives / Tertiary carboxylic acid amide / Amino acid or derivatives / Carboxamide group / Carboxylic acid derivative / Organopnictogen compound / Organic oxygen compound / Primary amine
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serotonin:sodium symporter activity
Specific Function
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
Gene Name
SLC6A4
Uniprot ID
P31645
Uniprot Name
Sodium-dependent serotonin transporter
Molecular Weight
70324.165 Da
References
  1. Leo RJ, Brooks VL: Clinical potential of milnacipran, a serotonin and norepinephrine reuptake inhibitor, in pain. Curr Opin Investig Drugs. 2006 Jul;7(7):637-42. [PubMed:16869117]
  2. Moret C, Charveron M, Finberg JP, Couzinier JP, Briley M: Biochemical profile of midalcipran (F 2207), 1-phenyl-1-diethyl-aminocarbonyl-2-aminomethyl-cyclopropane (Z) hydrochloride, a potential fourth generation antidepressant drug. Neuropharmacology. 1985 Dec;24(12):1211-9. [PubMed:3005901]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Norepinephrine:sodium symporter activity
Specific Function
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A2
Uniprot ID
P23975
Uniprot Name
Sodium-dependent noradrenaline transporter
Molecular Weight
69331.42 Da
References
  1. Leo RJ, Brooks VL: Clinical potential of milnacipran, a serotonin and norepinephrine reuptake inhibitor, in pain. Curr Opin Investig Drugs. 2006 Jul;7(7):637-42. [PubMed:16869117]
  2. Moret C, Charveron M, Finberg JP, Couzinier JP, Briley M: Biochemical profile of midalcipran (F 2207), 1-phenyl-1-diethyl-aminocarbonyl-2-aminomethyl-cyclopropane (Z) hydrochloride, a potential fourth generation antidepressant drug. Neuropharmacology. 1985 Dec;24(12):1211-9. [PubMed:3005901]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated cation channel activity
Specific Function
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein plays a key role in synaptic p...

Components:
References
  1. Kohno T, Kimura M, Sasaki M, Obata H, Amaya F, Saito S: Milnacipran inhibits glutamatergic N-methyl-D-aspartate receptor activity in spinal dorsal horn neurons. Mol Pain. 2012 Jun 19;8:45. doi: 10.1186/1744-8069-8-45. [PubMed:22716121]
  2. Shuto S, Takada H, Mochizuki D, Tsujita R, Hase Y, Ono S, Shibuya N, Matsuda A: (+/-)-(Z)-2-(aminomethyl)-1-phenylcyclopropanecarboxamide derivatives as a new prototype of NMDA receptor antagonists. J Med Chem. 1995 Jul 21;38(15):2964-8. [PubMed:7636857]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Paris BL, Ogilvie BW, Scheinkoenig JA, Ndikum-Moffor F, Gibson R, Parkinson A: In vitro inhibition and induction of human liver cytochrome p450 enzymes by milnacipran. Drug Metab Dispos. 2009 Oct;37(10):2045-54. doi: 10.1124/dmd.109.028274. Epub 2009 Jul 16. [PubMed:19608694]

Drug created on October 21, 2007 16:23 / Updated on August 26, 2018 02:00