Rupatadin

Structural formula
General
Non-proprietary name	Rupatadin
other names	8-Chloro-6,11-dihydro-11- [1 - [(5-methyl-3-pyridinyl) methyl] 4-piperidinylidene] -5 H -benzo- [5,6] -cyclohepta- [1,2 b ] pyridine ( IUPAC )
Molecular formula	C 26 H 26 ClN 3
External identifiers / databases
EC number	825-304-8
ECHA InfoCard	100.260.389
PubChem	133017
ChemSpider	117388
DrugBank	DB11614
Wikidata	Q423450
Drug information
ATC code	R06 AX28
Drug class	H 1 antihistamine
properties
Molar mass	415.97 g · mol -1 (rupatadine) ; 525.34 g · mol -1 (rupatadine · trihydrochloride) ;
Melting point	58-61 ° C (rupatadine) ; 213–217 ° C (rupatadine trihydrochloride) ;
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling ; no classification available
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Rupatadine (trade name: Urtimed, manufacturer: J. Uriach y Cia , SA, Spain) is a chlorine-containing heterocyclic compound that belongs to the class of azines (here pyridine derivatives). As a medicinal substance , rupatadine belongs to the group of H ₁ antihistamines , which is used for the symptomatic treatment of allergic rhinitis (hay fever) and chronic urticaria (hives). As a new antihistamine, Rupatadine is a substance that not only has a strong and specific antihistaminergic activity, but also a PAF (platelet activating factor) antagonistic effect and thus a dual mechanism of action. It can be used in the form of tablets in adults and children and adolescents from 12 years of age. An oral solution is available for children aged 2-11.

chemistry

Rupatadine belongs to the group of pyridine and piperidine derivatives. It is found in the preparation Rupafin® and Urtimed® as a salt of fumaric acid . The chemical structure of rupatadine contains two functional groups: the piperidinyl group , which is responsible for the antihistaminergic activity at the H ₁ receptor, and the lutidinyl group ( dimethylpyridinyl group , occurs twice), on which the activity at the PAF receptors is based. The structure is somewhat similar to loratadine .

Mechanism of action

Rupatadine works on the H ₁ and PAF receptors without prior metabolism , so it is not a prodrug . Compared to other antihistamines such as levocetirizine or fexofenadine, rupatadine has a higher affinity for the H ₁ receptor. At the same time rupatadine blocks the PAF receptors. This property could be important in allergic, PAF-mediated inflammatory processes as well as in manifestations of bronchial hyperactivity. In patients with anaphylaxis , PAF is increased and correlates with the severity of the reaction, especially in the case of a fatal peanut allergy. Due to its physicochemical properties, rupatadine can be described as a new, non- sedating, long-acting H ₁ antihistamine with a dual mode of action.

Side effects

The most common side effects observed were somnolence , headache and fatigue. However, studies on traffic safety showed no changes in psychomotor functions compared to placebo . Rupatadine has no influence on the electrocardiogram (ECG) (QT interval) even in doses that are up to 10 times the therapeutic doses .

Interactions

Rupatadine is metabolized via the isoenzyme CYP3A4 . Concomitant use of CYP3A4 inhibitors such as ketoconazole , erythromycin or grapefruit juice can lead to an increase in systemic rupatadine exposure . This was not associated with an increase in side effects. The risk of interactions with statins , most of which are metabolized by CYP3A4, is unknown.

literature

Merlos M, Giral M, Balsa D et al .: Rupatadine, a new potent, orally active dual antagonist of histamine and platelet-activating factor (PAF) . In: J Pharmacol Exp Ther 1997; 280 (1): 114-121. PMID 8996188 . Full text. Retrieved August 16, 2008.
Barron S et al .: Inhibitory activity of rupatadine on pro-inflammatory cytokine production, relationship with binding activity . In: Methods Find Exp Clin Pharmacol 2005; 27 (Suppl 2): 161 (P-104).
Vadas P et al .: Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis . In: N Engl J Med 2008; 358: 28-35. PMID 18172172 . Full text. Retrieved August 16, 2008.
Queralt M et al .: Dual effect of a new compound, rupatadine, on edema induced by platelet-activating factor and histamine in dogs: Comparison with antihistamines and PAF antagonists . In: Drug Dev Res 1996; 39 (1): 12-18. doi : 10.1002 / (SICI) 1098-2299 (19960901) 39: 1% 3C12 :: AID-DDR2% 3E3.3.CO; 2-3

Individual evidence

^ ^A ^b The Merck Index : An Encyclopedia of Chemicals, Drugs, and Biologicals , 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; P. 1433, ISBN 978-0-911910-00-1 .
↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.

[MERCK_Index-1] A ^b The Merck Index : An Encyclopedia of Chemicals, Drugs, and Biologicals , 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; P. 1433, ISBN 978-0-911910-00-1 .

[NV-2] This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.