Pimobendan | CAS# 74150-27-9 (free base) | PDE3 inhibitor

MedKoo Cat#: 319513 | Name: Pimobendan

Description:

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

Pimobendan is a veterinary medication. Pimobendan is both a calcium sensitizer and a selective inhibitor of phosphodiesterase III (PDE3) with positive inotropic and vasodilator effects. Pimobendan is used in the management of heart failure in dogs, most commonly caused by myxomatous mitral valve disease (also previously known as endocardiosis), or dilated cardiomyopathy.Research has shown that pimobendan increases survival time and improves quality of life in canine patients with congestive heart failure secondary to mitral valve disease when compared with benazepril, an angiotensin-converting-enzyme (ACE) inhibitor.

Chemical Structure

Pimobendan

CAS#74150-27-9 (free base)

Theoretical Analysis

MedKoo Cat#: 319513

Name: Pimobendan

CAS#: 74150-27-9 (free base)

Chemical Formula: C19H18N4O2

Exact Mass: 334.1430

Molecular Weight: 334.38

Elemental Analysis: C, 68.25; H, 5.43; N, 16.76; O, 9.57

Price and Availability

Size	Price	Availability
200mg	USD 90.00	Ready to ship
500mg	USD 150.00	Ready to ship
1g	USD 250.00	Ready to ship
2g	USD 400.00	Ready to ship
5g	USD 750.00	Ready to ship
10g	USD 1,250.00	Ready to ship
20g	USD 2,150.00	Ready to ship

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Related CAS #

77469-98-8 (HCl) 74150-27-9 (free base)

Synonym

UD-CG115; UD CG115; UD-CG 115; UD-CG-115; Pimobendan; pimobendane. Trade name: Vetmedin and Acardi

IUPAC/Chemical Name

3-[2-(4-methoxyphenyl)-3H-benzimidazol-5-yl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one

InChi Key

GLBJJMFZWDBELO-UHFFFAOYSA-N

InChi Code

InChI=1S/C19H18N4O2/c1-11-9-17(24)22-23-18(11)13-5-8-15-16(10-13)21-19(20-15)12-3-6-14(25-2)7-4-12/h3-8,10-11H,9H2,1-2H3,(H,20,21)(H,22,24)

SMILES Code

O=C1CC(C)C(C2=CC=C3C(NC(C4=CC=C(OC)C=C4)=N3)=C2)=NN1

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, not in water

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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#CRB70424

QC Data

View QC data: current batch, Lot#CRB70424

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Pimobendan (UD-CG115) is a selective inhibitor of PDE3 with IC50 of 0.32 μM

In vitro activity:

To determine the contribution of the various phosphodiesterase (PDE) isozymes to the regulation of the L-type calcium current (ICa(L)) in the human myocardium, we investigated the effect of selective and non-selective PDE inhibitors on ICa(L) in single human atrial cells and rabbit atrial myocytes by use of the whole-cell patch-clamp method. In human atrial cells, 100 microM pimobendan increased ICa(L) (evoked by depolarization to +10 mV from a holding potential of -40 mV) by 250.4 +/- 45.0% (n = 15), with the concentration for half-maximal stimulation (EC50) being 1.13 microM. ICa(L) was increased by 100 microM UD-CG 212 by 174.5 +/- 30.2% (n = 10) with an EC50 value of 1.78 microM in human atrial cells. These two agents inhibit PDE III selectively. In rabbit atrial cells, ICa(L) at +10 mV was increased by 22.1 +/- 9.0% by UD-CG 212 (n = 10) and by 67.4 +/- 12.0% (n = 10) by pimobendan (each at 100 microM). These values were significantly lower than those obtained in human atrial cells (P < 0.0001). PDE IV might contribute significantly to the regulation of intracellular cyclic AMP in human myocardium when PDE III is already inhibited or when the myocardium is under beta-adrenoceptor-mediated stimulation. Reference: Br J Pharmacol. 1997 Aug;121(8):1549-56. https://pubmed.ncbi.nlm.nih.gov/9283687/

In vivo activity:

This study was designed to examine the effects of pimobendan in a murine model of viral myocarditis in relation to proinflammatory cytokine production and nitric oxide (NO) synthesis by inducible NO synthase (iNOS) in the heart. DBA/2 mice were inoculated with the encephalomyocarditis virus. To observe its effect on survival up to 14 days, pimobendan (0.1 mg/kg or 1 mg/kg) or vehicles were given from the day of virus inoculation (day 0) orally once daily. The effects of pimobendan on histological changes, cytokine production, NO production and iNOS gene expression in the heart were studied in mice treated either with pimobendan, 1 mg/kg or with vehicles only, and sacrificed seven days after virus inoculation. The survival of mice improved in a dose-dependent fashion such that a significant difference (p < 0.02) was found between the higher-dose pimobendan group (20 of 30 [66.7%]) and the control group (11 of 30 [36.7%]). Histological scores for cellular infiltration (1.1+/-0.1 vs. 2.0+/-0.0, p < 0.001), intracardiac tumor necrosis factor (TNF)-alpha (18.2+/-1.8 vs. 35.8+/-4.2 pg/mg heart, p < 0.001) and interleukin (IL)-1beta (9.3 +/-1.2 vs. 26.6+/-7.1 pg/mg heart, p < 0.01) were significantly lower in the mice given pimobendan versus those of the control mice. Interleukin-6 levels (7.1+/-0.8 vs. 9.2+/-1.9 pg/mg heart) were also lower in the mice treated with pimobendan. Furthermore, intracardiac NO production was significantly (p < 0.001) less in the pimobendan group (0.165+/-0.004 nmol/mg heart) than in the control group (0.291+/-0.051 nmol/mg heart), and intracardiac iNOS gene expression in the mice given pimobendan was 74% lower than it was in the control animals (p < 0.01). These findings suggest that the beneficial effects of pimobendan in viral myocarditis are partially mediated by the inhibition of both proinflammatory cytokine production and NO synthesis by iNOS. Reference: J Am Coll Cardiol. 1999 Apr;33(5):1400-7. https://pubmed.ncbi.nlm.nih.gov/10193745/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	50.0	149.50

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 334.38 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.

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:

1. Iwasaki A, Matsumori A, Yamada T, Shioi T, Wang W, Ono K, Nishio R, Okada M, Sasayama S. Pimobendan inhibits the production of proinflammatory cytokines and gene expression of inducible nitric oxide synthase in a murine model of viral myocarditis. J Am Coll Cardiol. 1999 Apr;33(5):1400-7. doi: 10.1016/s0735-1097(98)00692-5. PMID: 10193745. 2. Suzuki S, Fukushima R, Ishikawa T, Hamabe L, Aytemiz D, Huai-Che H, Nakao S, Machida N, Tanaka R. The effect of pimobendan on left atrial pressure in dogs with mitral valve regurgitation. J Vet Intern Med. 2011 Nov-Dec;25(6):1328-33. doi: 10.1111/j.1939-1676.2011.00800.x. Epub 2011 Sep 21. PMID: 22092624. 3. Kajimoto K, Hagiwara N, Kasanuki H, Hosoda S. Contribution of phosphodiesterase isozymes to the regulation of the L-type calcium current in human cardiac myocytes. Br J Pharmacol. 1997 Aug;121(8):1549-56. doi: 10.1038/sj.bjp.0701297. PMID: 9283687; PMCID: PMC1564856.

In vitro protocol:

1. Kajimoto K, Hagiwara N, Kasanuki H, Hosoda S. Contribution of phosphodiesterase isozymes to the regulation of the L-type calcium current in human cardiac myocytes. Br J Pharmacol. 1997 Aug;121(8):1549-56. doi: 10.1038/sj.bjp.0701297. PMID: 9283687; PMCID: PMC1564856.

In vivo protocol:

1: Boyle KL, Leech E. A review of the pharmacology and clinical uses of pimobendan. J Vet Emerg Crit Care (San Antonio). 2012 Aug;22(4):398-408. doi: 10.1111/j.1476-4431.2012.00768.x. Review. PubMed PMID: 22928748. 2: Bowles D, Fry D. Pimobendan and its use in treating canine congestive heart failure. Compend Contin Educ Vet. 2011 Nov;33(11):E1. Review. PubMed PMID: 22101450. 3: Boswood A. Current use of pimobendan in canine patients with heart disease. Vet Clin North Am Small Anim Pract. 2010 Jul;40(4):571-80. doi: 10.1016/j.cvsm.2010.04.003. Review. PubMed PMID: 20610012. 4: Gordon SG, Miller MW, Saunders AB. Pimobendan in heart failure therapy--a silver bullet? J Am Anim Hosp Assoc. 2006 Mar-Apr;42(2):90-3. Review. PubMed PMID: 16527909. 5: Fuentes VL. Use of pimobendan in the management of heart failure. Vet Clin North Am Small Anim Pract. 2004 Sep;34(5):1145-55. Review. PubMed PMID: 15325474. 6: Kubo SH. Effects of pimobendan on exercise tolerance and quality of life in patients with heart failure. Cardiology. 1997;88 Suppl 2:21-7. Review. PubMed PMID: 9142432. 7: Fitton A, Brogden RN. Pimobendan. A review of its pharmacology and therapeutic potential in congestive heart failure. Drugs Aging. 1994 May;4(5):417-41. Review. PubMed PMID: 8043944. 8: Kubo SH. Inotropic agents with calcium-sensitizing properties: clinical and hemodynamic effects of pimobendan. Coron Artery Dis. 1994 Feb;5(2):119-26. Review. PubMed PMID: 8180743. 9: Hagemeijer F. Calcium sensitization with pimobendan: pharmacology, haemodynamic improvement, and sudden death in patients with chronic congestive heart failure. Eur Heart J. 1993 Apr;14(4):551-66. Review. PubMed PMID: 8472722.