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MedKoo Cat#: 326992 | Name: Bicifadine HCl

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Bicifadine, also known as DOV-220075, CL 220,075, is a SNDR inhibitor potentially for the treatment of lower back pain. Bicifadine has a non-opioid, non-NSAID mechanism for the treatment of pain, which should have less abuse potential than opioid drugs and less propensity to cause gastric ulcers than NSAID drugs. While the drug is purported to be a serotonin (SERT) and noradrenaline transporter (NET) inhibitor, it also has effects at the dopamine transporter (DAT), effectively making it a broad-spectrum monoamine transporter inhibitor or "triple reuptake inhibitor."

Chemical Structure

Bicifadine HCl
Bicifadine HCl
CAS#66504-75-4 (HCl)

Theoretical Analysis

MedKoo Cat#: 326992

Name: Bicifadine HCl

CAS#: 66504-75-4 (HCl)

Chemical Formula: C12H16ClN

Exact Mass: 0.0000

Molecular Weight: 209.72

Elemental Analysis: C, 68.73; H, 7.69; Cl, 16.90; N, 6.68

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Related CAS #
71195-57-8 (free base) 66504-75-4 (HCl)
Synonym
Bicifadine hydrochloride; DOV-220075; DOV 220075; DOV220075; CL 220,075; CL220,075.
IUPAC/Chemical Name
(1R,5S)-1-(p-tolyl)-3-azabicyclo[3.1.0]hexane hydrochloride
InChi Key
OTZOPAFTLUOBOM-LYCTWNKOSA-N
InChi Code
InChI=1S/C12H15N.ClH/c1-9-2-4-10(5-3-9)12-6-11(12)7-13-8-12;/h2-5,11,13H,6-8H2,1H3;1H/t11-,12+;/m1./s1
SMILES Code
CC1=CC=C([C@]23CNC[C@@]2([H])C3)C=C1.[H]Cl
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Related CAS# 71195-57-8 (Bicifadine free base) 66504-75-4 (Bicifadine hydrochloride)
Product Data
Product Data
Instruction
View handling instruction
Biological target:
5-HT and dopamine re-uptake inhibitor.
In vitro activity:
The primary enzymes responsible for the primary metabolism of bicifadine in humans are MAO-B and CYP2D6. Reference: Erickson DA, Hollfelder S, Tenge J, Gohdes M, Burkhardt JJ, Krieter PA. In vitro metabolism of the analgesic bicifadine in the mouse, rat, monkey, and human. Drug Metab Dispos. 2007 Dec;35(12):2232-41. doi: 10.1124/dmd.107.016055. Epub 2007 Sep 19. PMID: 17881661.
In vivo activity:
Bicifadine potently suppressed pain responses in both the Randall-Selitto and kaolin models of acute inflammatory pain and in the phenyl-p-quinone-induced and colonic distension models of persistent visceral pain. Unlike many transport inhibitors, bicifadine was potent and completely efficacious in both phases of the formalin test in both rats and mice. Bicifadine also normalized the nociceptive threshold in the complete Freund's adjuvant model of persistent inflammatory pain and suppressed mechanical and thermal hyperalgesia and mechanical allodynia in the spinal nerve ligation model of chronic neuropathic pain. Mechanical hyperalgesia was also reduced by bicifadine in the streptozotocin model of neuropathic pain. Administration of the D(2) receptor antagonist (-)-sulpiride reduced the effects of bicifadine in the mechanical hyperalgesia assessment in rats with spinal nerve ligations. These results indicate that bicifadine is a functional triple reuptake inhibitor with antinociceptive and antiallodynic activity in acute, persistent, and chronic pain models, with activation of dopaminergic pathways contributing to its antihyperalgesic actions. Reference: Basile AS, Janowsky A, Golembiowska K, Kowalska M, Tam E, Benveniste M, Popik P, Nikiforuk A, Krawczyk M, Nowak G, Krieter PA, Lippa AS, Skolnick P, Koustova E. Characterization of the antinociceptive actions of bicifadine in models of acute, persistent, and chronic pain. J Pharmacol Exp Ther. 2007 Jun;321(3):1208-25. doi: 10.1124/jpet.106.116483. Epub 2007 Feb 26. PMID: 17325229.
Solvent mg/mL mM comments
Solubility
DMSO 21.0 100.00
Water 21.0 100.00
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 209.72 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
Erickson DA, Hollfelder S, Tenge J, Gohdes M, Burkhardt JJ, Krieter PA. In vitro metabolism of the analgesic bicifadine in the mouse, rat, monkey, and human. Drug Metab Dispos. 2007 Dec;35(12):2232-41. doi: 10.1124/dmd.107.016055. Epub 2007 Sep 19. PMID: 17881661.
In vitro protocol:
Erickson DA, Hollfelder S, Tenge J, Gohdes M, Burkhardt JJ, Krieter PA. In vitro metabolism of the analgesic bicifadine in the mouse, rat, monkey, and human. Drug Metab Dispos. 2007 Dec;35(12):2232-41. doi: 10.1124/dmd.107.016055. Epub 2007 Sep 19. PMID: 17881661.
In vivo protocol:
(1). Nicholson KL, Balster RL, Golembiowska K, Kowalska M, Tizzano JP, Skolnick P, Basile AS. Preclinical evaluation of the abuse potential of the analgesic bicifadine. J Pharmacol Exp Ther. 2009 Jul;330(1):236-48. doi: 10.1124/jpet.109.150540. Epub 2009 Apr 8. PMID: 19357320; PMCID: PMC3202431.’ (2). Basile AS, Janowsky A, Golembiowska K, Kowalska M, Tam E, Benveniste M, Popik P, Nikiforuk A, Krawczyk M, Nowak G, Krieter PA, Lippa AS, Skolnick P, Koustova E. Characterization of the antinociceptive actions of bicifadine in models of acute, persistent, and chronic pain. J Pharmacol Exp Ther. 2007 Jun;321(3):1208-25. doi: 10.1124/jpet.106.116483. Epub 2007 Feb 26. PMID: 17325229.
1: Srinivas NR, Ahlawat P. Prediction of human pharmacokinetic parameters using animal data and principles of allometry. A case using bicifadine, a non-narcotic analgesic, as an example. Arzneimittelforschung. 2009;59(12):625-30. doi: 10.1055/s-0031-1296450. Review. PubMed PMID: 20108647. 2: Nicholson KL, Balster RL, Golembiowska K, Kowalska M, Tizzano JP, Skolnick P, Basile AS. Preclinical evaluation of the abuse potential of the analgesic bicifadine. J Pharmacol Exp Ther. 2009 Jul;330(1):236-48. doi: 10.1124/jpet.109.150540. Epub 2009 Apr 8. PubMed PMID: 19357320; PubMed Central PMCID: PMC3202431. 3: Zhang M, Jovic F, Vickers T, Dyck B, Tamiya J, Grey J, Tran JA, Fleck BA, Pick R, Foster AC, Chen C. Studies on the structure-activity relationship of bicifadine analogs as monoamine transporter inhibitors. Bioorg Med Chem Lett. 2008 Jul 1;18(13):3682-6. doi: 10.1016/j.bmcl.2008.05.077. Epub 2008 May 23. PubMed PMID: 18539031. 4: Krieter PA, Gohdes M, Musick TJ, Duncanson FP, Bridson WE. Pharmacokinetics, disposition, and metabolism of bicifadine in humans. Drug Metab Dispos. 2008 Feb;36(2):252-9. Epub 2007 Nov 8. PubMed PMID: 17991768. 5: Musick TJ, Gohdes M, Duffy A, Erickson DA, Krieter PA. Pharmacokinetics, disposition, and metabolism of bicifadine in the mouse, rat, and monkey. Drug Metab Dispos. 2008 Feb;36(2):241-51. Epub 2007 Nov 8. PubMed PMID: 17991767. 6: Erickson DA, Hollfelder S, Tenge J, Gohdes M, Burkhardt JJ, Krieter PA. In vitro metabolism of the analgesic bicifadine in the mouse, rat, monkey, and human. Drug Metab Dispos. 2007 Dec;35(12):2232-41. Epub 2007 Sep 19. PubMed PMID: 17881661. 7: Basile AS, Janowsky A, Golembiowska K, Kowalska M, Tam E, Benveniste M, Popik P, Nikiforuk A, Krawczyk M, Nowak G, Krieter PA, Lippa AS, Skolnick P, Koustova E. Characterization of the antinociceptive actions of bicifadine in models of acute, persistent, and chronic pain. J Pharmacol Exp Ther. 2007 Jun;321(3):1208-25. Epub 2007 Feb 26. PubMed PMID: 17325229. 8: Xu F, Murry JA, Simmons B, Corley E, Fitch K, Karady S, Tschaen D. Stereocontrolled synthesis of trisubstituted cyclopropanes: expedient, atom-economical, asymmetric syntheses of (+)-Bicifadine and DOV21947. Org Lett. 2006 Aug 17;8(17):3885-8. PubMed PMID: 16898842. 9: McArdle P, Gilligan K, Cunningham D, Ryder A. Determination of the polymorphic forms of bicifadine hydrochloride by differential scanning calorimetry-thermogravimetric analysis, X-ray powder diffraction, attenuated total reflectance-infrared spectroscopy, and attenuated total reflectance-near-infrared spectroscopy. Appl Spectrosc. 2005 Nov;59(11):1365-71. PubMed PMID: 16316514. 10: Wang RI, Johnson RP, Lee JC, Waite EM. The oral analgesic efficacy of bicifadine hydrochloride in postoperative pain. J Clin Pharmacol. 1982 Apr;22(4):160-4. PubMed PMID: 7096604. 11: Epstein JW, Osterberg AC, Regan BA. Bicifadine: non-narcotic analgesic activity of 1-aryl-3-azabicyclo[3.1.0] hexanes. NIDA Res Monogr. 1982 Apr;41:93-8. PubMed PMID: 6811945.