Pimobendan

Structural formula
	1: 1 mixture of ( R ) -form (top) and ( S ) -form (bottom)
General
Non-proprietary name	Pimobendan
other names	( RS ) -6- [2- (4-methoxyphenyl) -1 H -benzoimidazol-5-yl] -5-methyl-4,5-dihydro-2 H -pyridazin-3-one; DL -6- [2- (4-methoxyphenyl) -1 H -benzoimidazol-5-yl] -5-methyl-4,5-dihydro-2 H -pyridazin-3-one; (±) -6- [2- (4-methoxyphenyl) -1 H -benzoimidazol-5-yl] -5-methyl-4,5-dihydro-2 H -pyridazin-3-one; rac -6- [2- (4-methoxyphenyl) -1 H -benzoimidazol-5-yl] -5-methyl-4,5-dihydro-2 H -pyridazin-3-one;
Molecular formula	C 19 H 18 N 4 O 2 (pimobendan) ; C 19 H 18 N 4 O 2 HCl (pimobendan hydrochloride) ;
Brief description	white to slightly yellowish, hygroscopic powder
External identifiers / databases
EC number	640-420-7
ECHA InfoCard	100.168.193
PubChem	4823
ChemSpider	4657
Wikidata	Q414351
Drug information
ATC code	Q C01CE90
Drug class	Inodilator
Mechanism of action	Calcium sensitizer
properties
Molar mass	334.37 g · mol -1
Melting point	242 ° C (pimobendan) ; 311 ° C (decomposition) (pimobendan hydrochloride) ;
solubility	practically insoluble in water, slightly soluble in dimethylformamide , sparingly soluble in acetone and methanol
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances danger
H and P phrases	H: 301
	P: 301 + 310 + 330
Toxicological data	950 mg kg −1 ( LD 50 , rat , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Pimobendan is a medicinal substance that is only approved as a cardiovascular agent for animals. Alongside levosimendan, it is the only representative from the calcium sensitizer group to date .

Mode of action

The drug works through two mechanisms. The main effect is on the increase of the contractility of the cardiac muscle by means of an increased sensitivity for calcium - ions caused. Inhibiting the activity of the enzyme phosphodiesterase 3 has the same effect and also has a vasodilating effect . As a result of this positive inotropic and vasodilatory effect, the active ingredient is also known as an inodilator .

Pharmacokinetics

It is administered orally by means of divisible chewable tablets or capsules available in various doses . About 60 percent of the active ingredient is absorbed from the intestine and quickly distributed in the tissue ( volume of distribution : 2.6 l / kg; mean binding to plasma proteins : 93%). By oxidative demethylation , the pharmacologically active arise metabolites of the drug. It is excreted with the faeces. The half-life of the major metabolite in plasma is approximately 2 hours.

application areas

The drug was originally intended as a therapeutic agent for dilated cardiomyopathy in dogs and is the drug of choice here. As a result of its good vasodilatory properties, it is also becoming increasingly popular in the treatment of heart valve diseases , especially in the treatment of valve endocardiosis .

Contraindications

Due to its mode of action, the drug must not be used in cardiac diseases in which an increase in the cardiac output volume is opposed by functional or anatomical obstacles (e.g. aortic stenosis , pulmonary stenosis ). It is also not to be used in the presence of hypertrophic cardiomyopathy and in the presence of severe liver dysfunction .

Side effects

The occurrence of tachycardia (rapid heartbeat) has been described. In addition, gastrointestinal symptoms, e.g. B. Vomiting and diarrhea occur. In humans , the drug is not used in Europe and America due to possible severe intolerance ( sudden cardiac death ), but it is approved as a human medicinal product in Japan .

So far, Pimobendan has only been approved for dogs in Germany .

Stereoisomerism

Pimobendan has a stereocenter and is therefore chiral . There are two stereoisomers , the ( R ) form and the ( S ) form. The drug used is racemic pimobendan, i.e. a 1: 1 mixture of the ( R ) and ( S ) enantiomers .

Trade names

Veterinary medicine: Cardisure , Vetmedin ; as a combination preparation with benazepril : Fortekor Plus

Web links

Entry on Pimobendan at Vetpharm, accessed on August 4, 2012.

Individual evidence

↑ ^a ^b ^c ^d data sheet PIMOBENDAN CRS (PDF) at EDQM , accessed on May 1, 2009.
^ The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, ISBN 978-0-911910-00-1 , p. 1281.
↑ ^a ^b Data sheet Pimobendan, ≥98% (HPLC) from Sigma-Aldrich , accessed on October 31, 2016 ( PDF ).

[Ph._Eur.-1] ta sheet PIMOBENDAN CRS (PDF) at EDQM , accessed on May 1, 2009.

[MerckIndex-2] The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, ISBN 978-0-911910-00-1 , p. 1281.

[Sigma-3] Data sheet Pimobendan, ≥98% (HPLC) from Sigma-Aldrich , accessed on October 31, 2016 ( PDF ).