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			{{Short description|Chemical compound}}
	{{Drugbox
			{{Use dmy dates|date=April 2024}}
	| drug_name = Pimobendan
			{{cs1 config |name-list-style=vanc |display-authors=6}}
	| IUPAC_name = (''RS'')-6--5-methyl-4,5-dihydropyridazin-3(2''H'')-one
			{{Infobox drug
	| image = Pimobendan skeletal.svg
			| Verifiedfields = changed
	| imagename = 1 : 1 mixture (racemate)
			| Watchedfields = changed
	| width = 200px
			| verifiedrevid = 408556559
	| CAS_number = 74150-27-9
			| image = Pimobendan skeletal.svg
	| CAS_supplemental =
			| width = 200
	| ATCvet = yes
			| alt =
	| ATC_prefix = C01
			| image2 = Pimobendan.jpg
	| ATC_suffix = CE90
			| chirality = ]
	| ATC_supplemental =
	| PubChem = 4823
			<!--Clinical data-->
	| DrugBank =
			| tradename = Vetmedin, others
	| KEGG = D01133
			| Drugs.com = {{drugs.com|international|pimobendan}}
	| chemical_formula =
			| DailyMedID = Pimobendan
	| C=19 | H=18 | N=4 | O=2
			| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
	| molecular_weight = 334.37 g/mol
			| pregnancy_category =
	| smiles = CC1CC(=O)NN=C1C2=CC3=C(C=C2)N=C(N3)C4=CC=C(C=C4)OC
			| routes_of_administration = ]
	| bioavailability = 60 to 65%
			| ATCvet = yes
	| protein_bound =
			| ATC_prefix = C01
	| metabolism =
			| ATC_suffix = CE90
			| ATC_supplemental =
			| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
			| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
			| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
			| legal_US = Rx-only
			| legal_US_comment = <ref name="Vetmedin FDA label">{{cite web | title=Vetmedin- pimobendan tablet, chewable | website=DailyMed | date=19 October 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5441e5b2-cdc0-477a-bd9a-ec5f8d912281 | access-date=30 April 2024 | archive-date=15 April 2024 | archive-url=https://web.archive.org/web/20240415220638/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5441e5b2-cdc0-477a-bd9a-ec5f8d912281 | url-status=live }}</ref><ref name="Vetmedin CA1 FDA label">{{cite web | title=Vetmedin-CA1- pimobendan tablet, chewable | website=DailyMed | date=28 July 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b461035d-9c3c-42e2-ae1a-3ad611fd5e8d | access-date=30 April 2024}}</ref>
			| legal_status = Rx-only
			<!--Pharmacokinetic data-->
			| bioavailability = 60 to 65%
			| protein_bound =
			| metabolism =
	| elimination_half-life = 0.4 hours		| elimination_half-life = 0.4 hours
	| excretion = In feces		| excretion = In feces
	| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
			<!--Identifiers-->
	| pregnancy_US = <!-- A / B / C / D / X -->
			| CAS_number_Ref = {{cascite|correct|??}}
	| pregnancy_category=
			| CAS_number = 74150-27-9
	| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
			| PubChem = 4823
	| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
			| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
	| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
			| DrugBank =
	| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
			| UNII_Ref = {{fdacite|changed|FDA}}
	| legal_status = Rx-only
			| UNII = 34AP3BBP9T
	| routes_of_administration = Oral
			| KEGG_Ref = {{keggcite|correct|kegg}}
			| KEGG = D01133
			| ChEMBL_Ref = {{ebicite|changed|EBI}}
			| ChEMBL = 24646
			| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
			| ChemSpiderID = 4657
			<!--Chemical data-->
			| IUPAC_name = (''RS'')-6--5-methyl-4,5-dihydropyridazin-3(2''H'')-one
			| C=19 | H=18 | N=4 | O=2
			| smiles = CC1CC(=O)NN=C1C2=CC3=C(C=C2)N=C(N3)C4=CC=C(C=C4)OC
			| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
			| StdInChI = 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)
			| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
			| StdInChIKey = GLBJJMFZWDBELO-UHFFFAOYSA-N
	}}		}}
	'''Pimobendan''' (] is a veterinary medicaiton manufactured by ] under the trade names '''Vetmedin''' and '''Acardi''') or '''pimobendane'''. It is a calcium sensitizer with positive ] and ] effects. It is also a selective ] of ] III (]).		'''Pimobendan''' (], or '''pimobendane'''), sold under the brand name '''Vetmedin''' among others, is a veterinary medication. It is a calcium sensitizer and a selective inhibitor of ] (PDE3) with positive ] and ] effects.
	Pimobendan is used in the management of ] in dogs, most commonly caused by myxomatous mitral valve disease (also known as ]), or ].<ref>{{cite journal |author=Gordon SG, Miller MW, Saunders AB |title=Pimobendan in heart failure therapy—a silver bullet? |journal=J Am Anim Hosp Assoc |volume=42 |issue=2 |pages=90–3 |year=2006 |pmid=16527909 |doi= |url=http://www.jaaha.org/cgi/pmidlookup?view=long&pmid=16527909}}</ref> Research has shown that pimobendan increases survival time and improves quality of life in patients with ] secondary to mitral valve disease when compared with ], an ].<ref>{{cite journal |author=Häggström J, Boswood A, O'Grady M, ''et al.'' |title=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 |journal=J. Vet. Intern. Med. |volume= 22|issue= 5|pages= 1124|year=2008 |month=July |pmid=18638016 |doi=10.1111/j.1939-1676.2008.0150.x |url=}}</ref> Under the trade name Acardi, it is available for human use in ].<ref>{{cite web |url=http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=54 |title=Kusuri-no-Shiori Drug Information Sheet |date=April 2005 |publisher=RAD-AR Council, Japan |accessdate=2008-08-06}}</ref>		Pimobendan is used in the management of ] in dogs, most commonly caused by myxomatous mitral valve disease (also previously known as ]), or ].<ref>{{cite journal |vauthors=Gordon SG, Miller MW, Saunders AB |title=Pimobendan in heart failure therapy—a silver bullet? |journal=Journal of the American Animal Hospital Association |volume=42 |issue=2 |pages=90–3 |year=2006 |pmid=16527909 |doi= 10.5326/0420090 }}</ref> Research has shown that as a monotherapy, pimobendan increases survival time and improves quality of life in canine patients with ] secondary to mitral valve disease when compared with ], an ].<ref>{{cite journal |vauthors=Häggström J, Boswood A, O'Grady M, etal |title=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 |journal=J. Vet. Intern. Med. |volume= 22|issue= 5|pages= 1124–35|date=July 2008 |pmid=18638016 |doi=10.1111/j.1939-1676.2008.0150.x |citeseerx=10.1.1.661.3009|doi-access=free }}</ref> Under the brand name '''Acardi''', it is available for human use in Japan.<ref>{{cite web |url=http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=54 |title=Kusuri-no-Shiori Drug Information Sheet |date=April 2005 |publisher=RAD-AR Council, Japan |access-date=6 August 2008 |archive-date=22 July 2011 |archive-url=https://web.archive.org/web/20110722121958/http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=54 |url-status=live }}</ref> It is available as a ].<ref>{{cite web | title=FDA Approves First Generic Pimobendan for Management of Congestive Heart Failure in Dogs | website=U.S. ] (FDA) | date=25 April 2024 | url=https://www.fda.gov/animal-veterinary/cvm-updates/fda-approves-first-generic-pimobendan-management-congestive-heart-failure-dogs | access-date=30 April 2024 | archive-date=29 April 2024 | archive-url=https://web.archive.org/web/20240429214907/https://www.fda.gov/animal-veterinary/cvm-updates/fda-approves-first-generic-pimobendan-management-congestive-heart-failure-dogs | url-status=live }}</ref>
			== Medical uses ==
			Pimobendan is ] 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);<ref name="Vetmedin FDA label" /><ref>{{cite web | title = NADA 141-273 VETMEDIN Pimobendan Chewable Tablets Dogs | url = https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/832 }} {{PD-notice}}</ref> and for use with concurrent therapy for congestive heart failure (e.g.,furosemide, etc.) as appropriate on a case-by-case basis.<ref name="Vetmedin FDA label" /> It is also indicated for the delay of onset of congestive heart failure in dogs with Stage B2 preclinical myxomatous mitral valve disease (2019 ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs).<ref name="Vetmedin CA1 FDA label" /><ref>{{cite web | title = Application Number 141-556 Vetmedin®-CA1 (pimobendan) Chewable Tablets Dogs | url = https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/12512 | archive-url=https://web.archive.org/web/20221129220152/https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/12512 | archive-date=29 November 2022 }} {{PD-notice}}</ref><ref>{{cite web | title=FDA Conditionally Approves First Drug to Delay Onset of Congestive Heart Failure in Dogs | website=U.S. ] (FDA) | date=16 June 2022 | url=https://www.fda.gov/animal-veterinary/cvm-updates/fda-conditionally-approves-first-drug-delay-onset-congestive-heart-failure-dogs | access-date=30 April 2024 | archive-date=1 December 2023 | archive-url=https://web.archive.org/web/20231201201906/https://www.fda.gov/animal-veterinary/cvm-updates/fda-conditionally-approves-first-drug-delay-onset-congestive-heart-failure-dogs | url-status=live }} {{PD-notice}}</ref><ref>{{cite journal | vauthors = Keene BW, Atkins CE, Bonagura JD, Fox PR, Häggström J, Fuentes VL, Oyama MA, Rush JE, Stepien R, Uechi M | title = ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs | journal = Journal of Veterinary Internal Medicine | volume = 33 | issue = 3 | pages = 1127–1140 | date = May 2019 | pmid = 30974015 | pmc = 6524084 | doi = 10.1111/jvim.15488 }}</ref>
	==Mechanism of action==		==Mechanism of action==
			Pimobendan is a positive ], and its main function is to increase myocardial contractility. It sensitizes and increases the binding efficiency of cardiac troponin in the ] to the calcium ions that are already present in systole. In normal hearts it increases the consumption of oxygen and energy to the same degree as dobutamine but in diseased hearts it may not.<ref name="pmid1394935">{{cite journal | vauthors = Hata K, Goto Y, Futaki S, Ohgoshi Y, Yaku H, Kawaguchi O, Takasago T, Saeki A, Taylor TW, Nishioka T | title = Mechanoenergetic effects of pimobendan in canine left ventricles. Comparison with dobutamine | journal = Circulation | volume = 86 | issue = 4 | pages = 1291–301 | date = October 1992 | pmid = 1394935 | doi = 10.1161/01.cir.86.4.1291 }}</ref><ref name="pmid9476556">{{cite journal | vauthors = Goto Y, Hata K | title = Mechanoenergetic effect of pimobendan in failing dog hearts | journal = Heart and Vessels | volume = Suppl 12 | issue = | pages = 103–5 | date = 1997 | pmid = 9476556 | doi = | url = }}</ref> Pimobendan also causes peripheral ] by inhibiting the function of phosphodiesterase 3 (PDE3). This results in decreased resistance to blood flow through systemic arterioles, which decreases ] (decreases the failing heart's workload) and reduces the amount of mitral regurgitation.<ref>{{cite journal | vauthors = Verdouw PD, Hartog JM, Duncker DJ, Roth W, Saxena PR | title = Cardiovascular profile of pimobendan, a benzimidazole-pyridazinone derivative with vasodilating and inotropic properties | journal = European Journal of Pharmacology | volume = 126 | issue = 1–2 | pages = 21–30 | date = July 1986 | pmid = 2875884 | doi = 10.1016/0014-2999(86)90733-8 }}</ref><ref>{{cite journal | vauthors = Kanno N, Kuse H, Kawasaki M, Hara A, Kano R, Sasaki Y | title = Effects of pimobendan for mitral valve regurgitation in dogs | journal = The Journal of Veterinary Medical Science | volume = 69 | issue = 4 | pages = 373–7 | date = April 2007 | pmid = 17485924 | doi = 10.1292/jvms.69.373 | doi-access = free }}</ref>
	Pimobendan is a positive ]. It sensitizes and increases the binding efficiency of cardiac ] to the calcium ions that are already present without increasing the consumption of oxygen and energy. Pimobendan also causes peripheral ] by inhibiting the function of ]. This results in decreased pressure, translating into smaller cardiac ] and ] (decreases the failing heart's workload).
	==Pharmacokinetics==		==Pharmacokinetics==
	Pimobendan is absorbed rapidly when given via the oral route and has a ] of 60-65%. It is metabolized into its active form by the ]. The ] of pimobendan in the blood is 0.4 hours and the half-life of its metabolite is 2 hours. Elimination is by excretion in the bile and then feces. Pimobendan is 90–95% ] in circulation. This has implications in patients suffering from low blood protein levels (]/]) and with patients that are on concurrent therapies that are also highly protein bound.		Pimobendan is absorbed rapidly when given via the oral route and has a ] of 60–65%.<ref>{{Cite web |url=http://www.vetmedin.com/Vetmedin%20Insert_6-07.pdf |title=NADA 141-273, Approved by FDA Vetmedin (pimobendan) Chewable Tablets Cardiac drug for oral use in dogs only | date = 2007 | work = Boehringer Ingelheim Vetmedica, Inc. |access-date=2 December 2014 |archive-url=https://web.archive.org/web/20150206032743/http://vetmedin.com/Vetmedin%20Insert_6-07.pdf |archive-date=6 February 2015 |url-status=dead }}</ref> Food decreases the bioavailability of the aqueous solution although the effect on the tablet form is unknown.<ref>{{cite journal | vauthors = McManamey AK, DeFrancesco TC, Meurs KM, Papich MG | title = Pharmacokinetics of pimobendan after oral administration to dogs with myxomatous mitral valve disease | journal = Journal of Veterinary Internal Medicine | volume = 37 | issue = 6 | pages = 2003–2010 | date = November 2023 | pmid = 37776546 | pmc = 10658550 | doi = 10.1111/jvim.16891 }}</ref> 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 ].<ref name="pmid23116650">{{cite journal | vauthors = Hanzlicek AS, Gehring R, Kukanich B, Kukanich KS, Borgarelli M, Smee N, Olson EE, Margiocco M | title = Pharmacokinetics of oral pimobendan in healthy cats | journal = Journal of Veterinary Cardiology| volume = 14 | issue = 4 | pages = 489–96 | date = December 2012 | pmid = 23116650 | doi = 10.1016/j.jvc.2012.06.002 }}</ref> The ] 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% ] in circulation. This may have implications in patients with low blood protein levels (]/]) and in patients that are on concurrent therapies that are also highly protein bound.
	==Combinations==		==Combinations==
			{{Unreferenced section|date=April 2024}}
	Pimobendan is often used in combination with three other drugs to palliate dogs with heart disease and reduce clinical signs of disease. These are:
			Pimobendan is often used in combination with three other drugs to palliate dogs with heart failure (pulmonary edema, pleural effusion, ascites). These are:
	* ], a diuretic, to reduce ]. This can be given intravenously if the animal is in respiratory distress (6–8&nbsp;mg/kg), and then titrated down to the minimum dose required orally.
			* ], a diuretic, to reduce ] and effusion.
	* ], an ]. This has two actions, firstly, as a ], although its diuretic properties are small compared with those of furosemide. Secondly, it reduces aldosterone-mediated myocardial remodelling and fibrosis, slowing the progression of heart disease.
			* ], an ]. This has two actions, firstly, as a ], although its diuretic properties are small compared with those of furosemide. Secondly, it reduces aldosterone-mediated myocardial fibrosis, possibly slowing the progression of heart disease.
	*An ], often ] (trade name Enacard) or ] (Fortekor). These drugs inhibit the action of ], producing a balanced vasodilation, along with other favourable effects.
			* An ], often ] (brand name Enacard) or ] (Fortekor). These drugs inhibit the action of ], producing a balanced vasodilation, along with other potentially favorable effects.
			==Synthesis==
	Other drugs may also be used as required to manage certain ] that are often associated with heart disease.
			Patents:<ref>{{cite patent | inventor = Austel V, Diederen W, Eberlein W, Haarmann W, Heider J | country = DE | number = 2837161 | url = https://patents.google.com/patent/DE2837161A1/en?oq=DE+2837161 | title = 5-Alkyl:pyridazinyl substd. benzimidazole derivs. - useful as cardiovascular agents, antivirals, interferon inducers and ulcer inhibitors | pubdate = 6 March 1980 | assign = Boehringer Ingelheim Pharma GmbH and Co KG }}</ref><ref>{{cite patent | inventor = Austel V, Heider J, Eberlein W, Diederen W, Haarmann W | title = Pyridazinone-substituted benzimidazoles and salts | country = US | number = 4361563 | assign = Dr. Karl Thomae Gesellschaft Mit Beschrankter Haftung | gdate = 30 November 1982 }}</ref>]]
			The reaction between p-anisoyl chloride ('''1''') and ('''2''') gives 4--3-nitrophenyl]-3-methyl-4-oxobutanoic acid, ('''3'''). The reaction of this with hydrazine gives 5-methyl-6--3-oxo-4,5-dihydro-2H-pyridazine . Catalytic hydrogenation reduces the nitro group giving ('''4'''). cyclization of the resulting ortho amino amide by means of a strong acid leads to the formation of the corresponding benzimidazole. There is thus obtained pimobendan ('''5''').
	==Chemistry==
	Pimobendan can be synthesized beginning with ]:<ref>{{cite journal|doi=10.1002/jlcr.2580230806|author=Nicolas, C; Verny, M; Maurizis, J. C.; Payard, M.; Faurie, M|title=Synthesis of14C-bucromarone succinate and hydrochloride |journal=J. Labeled Cmpd. Radiopharm. | year= 1986 |volume=23 | pages=837}}</ref>
	:]
	==See also==
	*]
	==References==		==References==
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	==Further reading==		==Further reading==
	*{{cite journal |author=Lee JA, Allen DG |title=Calcium sensitisers |journal=BMJ |volume=300 |issue=6724 |pages=551–2 |year=1990 |month=March |pmid=2108746 |pmc=1662365 |doi=10.1136/bmj.300.6724.551}}		* {{cite journal |vauthors=Lee JA, Allen DG |title=Calcium sensitisers |journal=BMJ |volume=300 |issue=6724 |pages=551–2 |date=March 1990 |pmid=2108746 |pmc=1662365 |doi=10.1136/bmj.300.6724.551}}
			*
	==External links==
	*
	*
	*
	*Website about the QUEST study (reference 2) (http://www.questtrial.com)
	{{Phosphodiesterase inhibitors}}		{{Phosphodiesterase inhibitors}}
	{{Vasodilators used in cardiac diseases}}		{{Vasodilators used in cardiac diseases}}
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			{{Authority control}}
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