Pimobendan

Overview

Pimobendan (INN, or pimobendane), sold under the brand name Vetmedin among others, is a veterinary medication. It is a calcium sensitizer and a selective inhibitor of phosphodiesterase 3 (PDE3) with positive inotropic and vasodilator effects. WP

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 as a monotherapy, 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 ACE inhibitor. Under the brand name Acardi, it is available for human use in Japan. It is available as a generic medication.[1–4] WP

Uses, dosage and effects

Medical uses

Pimobendan is indicated for the management of the signs of mild, moderate, or severe congestive heart failure in dogs due to clinical myxomatous mitral valve disease (MMVD) or dilated cardiomyopathy (DCM); and for use with concurrent therapy for congestive heart failure (e.g., furosemide, etc.) as appropriate on a case-by-case basis. It is also indicated for the delay of onset of congestive heart failure in dogs with Stage B2 preclinical myxomatous mitral valve disease.[5–10] WP

Pharmacology

Mechanism of action

Pimobendan is a positive inotrope, and its main function is to increase myocardial contractility. It sensitizes and increases the binding efficiency of cardiac troponin in the myofibril to the calcium ions that are already present in systole. In healthy hearts, it elevates oxygen and energy consumption to a level comparable to that achieved with dobutamine; however, in pathological hearts, this effect may not occur. Pimobendan also causes peripheral vasodilation by inhibiting the function of phosphodiesterase 3 (PDE3). This results in decreased resistance to blood flow through systemic arterioles, which decreases afterload (decreases the failing heart's workload) and reduces the amount of mitral regurgitation.[11–14] WP

Pharmacokinetics

Pimobendan is absorbed rapidly when given via the oral route and has a bioavailability of 60–65%. Food decreases the bioavailability of the aqueous solution although the effect on the tablet form is unknown. It is metabolized into an active metabolite (desmethylpimobendan) by the liver. The parent compound, pimobendan, is a potent calcium sensitizer while desmethylpimobendan is a more potent phosphodiesterase III inhibitor. The half-life of pimobendan in the blood is 0.4 hours, and the half-life of its metabolite is two hours. Elimination is by excretion in the bile and then feces. Pimobendan is 90–95% bound to plasma proteins in circulation. This may have implications in patients with low blood protein levels (hypoproteinemia/hypoalbuminemia) and in patients that are on concurrent therapies that are also highly protein bound.[15][16][17] WP

Chemistry

Formula

C19H18N4O2 PC

CAS number

74150-27-9 PC

Molar mass (g/mol)

334.4 PC

IUPAC name (computed by PubChem)

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

SMILES

CC1CC(=O)NN=C1C2=CC3=C(C=C2)N=C(N3)C4=CC=C(C=C4)OC PC

InChIKey

GLBJJMFZWDBELO-UHFFFAOYSA-N PC

PubChem CID

4823

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Gordon SG, Miller MW, Saunders AB. Pimobendan in heart failure therapy—a silver bullet?. Journal of the American Animal Hospital Association. 2006. doi:10.5326/0420090 · PMID 16527909
2. Journal / agency Häggström J, Boswood A, O'Grady M, etal. Effect of Pimobendan or Benazepril Hydrochloride on Survival Times in Dogs with Congestive Heart Failure Caused by Naturally Occurring Myxomatous Mitral Valve Disease: The QUEST Study. J. Vet. Intern. Med. July 2008. doi:10.1111/j.1939-1676.2008.0150.x · PMID 18638016
3. Other Kusuri-no-Shiori Drug Information Sheet. April 2005
4. Journal / agency FDA Approves First Generic Pimobendan for Management of Congestive Heart Failure in Dogs. 25 April 2024
5. Journal / agency Vetmedin- pimobendan tablet, chewable. 19 October 2023
6. Journal / agency NADA 141-273 VETMEDIN Pimobendan Chewable Tablets Dogs
7. Journal / agency Vetmedin-CA1- pimobendan tablet, chewable. 28 July 2022
8. Journal / agency Application Number 141-556 Vetmedin®-CA1 (pimobendan) Chewable Tablets Dogs
9. Journal / agency FDA Conditionally Approves First Drug to Delay Onset of Congestive Heart Failure in Dogs. 16 June 2022
10. Journal / agency Keene BW, Atkins CE, Bonagura JD, Fox PR, Häggström J, Fuentes VL, Oyama MA, Rush JE, Stepien R, Uechi M. ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs. Journal of Veterinary Internal Medicine. May 2019. doi:10.1111/jvim.15488 · PMID 30974015 · PMC6524084
11. Journal / agency Hata K, Goto Y, Futaki S, Ohgoshi Y, Yaku H, Kawaguchi O, Takasago T, Saeki A, Taylor TW, Nishioka T. Mechanoenergetic effects of pimobendan in canine left ventricles. Comparison with dobutamine. Circulation. October 1992. doi:10.1161/01.cir.86.4.1291 · PMID 1394935
12. Journal / agency Goto Y, Hata K. Mechanoenergetic effect of pimobendan in failing dog hearts. Heart and Vessels. 1997. PMID 9476556
13. Journal / agency Verdouw PD, Hartog JM, Duncker DJ, Roth W, Saxena PR. Cardiovascular profile of pimobendan, a benzimidazole-pyridazinone derivative with vasodilating and inotropic properties. European Journal of Pharmacology. July 1986. doi:10.1016/0014-2999(86)90733-8 · PMID 2875884
14. Journal / agency Kanno N, Kuse H, Kawasaki M, Hara A, Kano R, Sasaki Y. Effects of pimobendan for mitral valve regurgitation in dogs. The Journal of Veterinary Medical Science. April 2007. doi:10.1292/jvms.69.373 · PMID 17485924
15. Other NADA 141-273, Approved by FDA Vetmedin (pimobendan) Chewable Tablets Cardiac drug for oral use in dogs only. 2007
16. Journal / agency McManamey AK, DeFrancesco TC, Meurs KM, Papich MG. Pharmacokinetics of pimobendan after oral administration to dogs with myxomatous mitral valve disease. Journal of Veterinary Internal Medicine. November 2023. doi:10.1111/jvim.16891 · PMID 37776546 · PMC10658550
17. Journal / agency Hanzlicek AS, Gehring R, Kukanich B, Kukanich KS, Borgarelli M, Smee N, Olson EE, Margiocco M. Pharmacokinetics of oral pimobendan in healthy cats. Journal of Veterinary Cardiology. December 2012. doi:10.1016/j.jvc.2012.06.002 · PMID 23116650

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.