Hydroxyzine

Structural formula
	1: 1 mixture of ( R ) -form (top) ; and ( S ) -form (bottom)
General
Non-proprietary name	Hydroxyzine
other names	( RS ) -5- [4- (4-chlorobenzhydryl) piperazin-1-yl] -3-oxapentan-1-ol ( IUPAC ); (±) -5- [4- (4-chlorobenzhydryl) piperazin-1-yl] -3-oxapentan-1-ol;
Molecular formula	C 21 H 27 ClN 2 O 2 (hydroxyzine) ; C 21 H 27 ClN 2 O 2 2 HCl (hydroxyzine dihydrochloride) ;
External identifiers / databases
EC number	200-693-1
ECHA InfoCard	100,000,630
PubChem	3658
ChemSpider	3531
DrugBank	DB00557
Wikidata	Q421937
Drug information
ATC code	N05 BB01
Drug class	Anxiolytics; Antihistamines; Ganglion blockers;
properties
Molar mass	374,90 g · mol -1 (hydroxyzine) ; 447.83 g · mol -1 (hydroxyzine · dihydrochloride) ;
Physical state	firmly
Melting point	193 ° C (hydroxyzine dihydrochloride)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 302-315-319-335
	P: 261-305 + 351 + 338
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Hydroxyzine (trade names: inter alia Atarax ^® , Vistaril; manufacturer: UCB ) is used to relieve anxiety in psychological and physical illnesses, to treat states of tension, emotional and mental restlessness, as well as problems falling and staying asleep . It is a drug from the group of histamine H1 antagonists of the first generation and can therefore be prescribed as a symptom of various skin diseases even in the case of severe itching , provided that a strongly sedating, psychotropic effect is desired at the same time.

application areas

Anxiety in the context of mental and other diseases
Fear of expectation z. B. before operations or examinations
States of excitement and tension
sleep disorders
Severe allergic diseases such as B. nettle rash (urticaria) and neurodermatitis

In clinical studies, the active ingredient also showed a pronounced regulatory effect on disturbed thought patterns in the context of mental disorders.

Mode of action

As a clinically effective antagonist, the drug hydroxyzine influences the messenger systems histamine H1 , 5-HT _2A receptors , dopamine D1 / D2 and the α1 adrenoceptors in the brain and the rest of the body. As a result, it has a pronounced anxiety-relieving, calming (on the emotional life and thinking) and sedating effect. Clinical studies after the market launch in the 1950s showed, in addition to a strong anti-anxiety effect, clear antipsychotic and thought disorders as well as obsessive-compulsive disorders that had a positive effect. Due to the simultaneous introduction of the typical neuroleptics , however, there was never an application for approval for these indications.

In addition, the active ingredient shows both nausea-reducing properties and, through a blockade of the histamine H1 receptors , a pronounced itch-relieving effect.

Hydroxyzine also acts in high concentrations as FIASMA (functional inhibitor of acid sphingomyelinase ).

Dismantling

The active substance is mainly metabolized to cetirizine by alcohol dehydrogenase and CYP3A4 / 5 . The simultaneous ingestion of substances that have an inhibitory effect on these enzymes leads to a significant increase in the plasma concentration of hydroxyzine.

Risks and Toxicity

The active substance crosses the placental barrier without any problems and then leads to a higher concentration of active substance in the fetus than in the mother. No animal tests were carried out with regard to carcinogenicity, but with regard to fetal damage. In rabbits and rats, malformations of fetuses and fetal abortions occurred above certain doses. Moderately severe intoxication occurs in adults at doses of 1.5–2.5 g of hydroxyzine .

Trade names

Monopreparations

AH 3 (D), Atarax (D, A, CH)

Individual evidence

^ The Merck Index. An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition. 2006, ISBN 0-911910-00-X , pp. 840-841.
↑ ^a ^b Data sheet Hydroxyzine dihydrochloride from Sigma-Aldrich , accessed on April 4, 2011 ( PDF ).
^ WS Schram: Use of hydroxyzine in psychosis. In: Dis Nerv Syst. 20, 1959, p. 126.
↑ Kaori Haraguchi et al: Prediction of drug-induced catalepsy (...). In: American Society for Pharmacology and Experimental Therapeutics . 1997.
↑ AM Snowman, SH Snyder: Cetirizine: actions on neurotransmitter receptors. In: Journal of Allergy and Clinical Immunology . 86 (6 Pt 2), December 1990, pp. 1025-1028.
↑ RP White, LD Boyajy: neuropharmacological comparison of atropine, scopolamine, banactyzine, diphenhydramine and hydroxyzine. In: Archives internationales de Pharmacodynamie et de Thérapie 127, 1960, pp. 260-273.
↑ N. Kubo, O. Shirakawa, T. Kuno, C. Tanaka: Antimuscarinic effects of antihistamines: quantitative evaluation by receptor-binding assay. In: Japanese Journal of Pharmacology . 43 (3), 1987, pp. 277-282.
^ Dan J. Stein: Textbook of Anxiety Disorders. American Psychiatric Pub., 2009, ISBN 978-1-58562-900-8 , p. 196 ( limited preview in Google book search).
↑ Y. Lamberty, AJ Gower: Hydroxyzine prevents isolation-induced vocalization in guinea pig pups: comparison with chlorpheniramine and immepip . In: Pharmacology, Biochemistry and Behavior . tape 79 , no. 1 , September 2004, p. 119-124 , doi : 10.1016 / j.pbb.2004.06.015 , PMID 15388291 .
^ WS Schram: Use of hydroxyzine in psychosis. In: Dis Nerv Syst. 20, 1959, p. 126.
↑ J. Kornhuber, M. Muehlbacher, S. Trapp, S. Pechmann, A. Friedl, M. Reichel, C. Mühle, L. Terfloth, T. Groemer, G. Spitzer, K. Liedl, E. Gulbins, P Tripal: Identification of novel functional inhibitors of acid sphingomyelinase . In: PLoS ONE . tape 6 , no. 8 , 2011, p. e23852 , doi : 10.1371 / journal.pone.0023852 .
↑ ^a ^b Yellow List. Retrieved July 14, 2017 .

[MerckIndex-1] The Merck Index. An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition. 2006, ISBN 0-911910-00-X , pp. 840-841.

[Sigma-2] Data sheet Hydroxyzine dihydrochloride from Sigma-Aldrich , accessed on April 4, 2011 ( PDF ).

[3] WS Schram: Use of hydroxyzine in psychosis. In: Dis Nerv Syst. 20, 1959, p. 126.

[4] Kaori Haraguchi et al: Prediction of drug-induced catalepsy (...). In: American Society for Pharmacology and Experimental Therapeutics . 1997.

[5] AM Snowman, SH Snyder: Cetirizine: actions on neurotransmitter receptors. In: Journal of Allergy and Clinical Immunology . 86 (6 Pt 2), December 1990, pp. 1025-1028.

[6] RP White, LD Boyajy: neuropharmacological comparison of atropine, scopolamine, banactyzine, diphenhydramine and hydroxyzine. In: Archives internationales de Pharmacodynamie et de Thérapie 127, 1960, pp. 260-273.

[7] N. Kubo, O. Shirakawa, T. Kuno, C. Tanaka: Antimuscarinic effects of antihistamines: quantitative evaluation by receptor-binding assay. In: Japanese Journal of Pharmacology . 43 (3), 1987, pp. 277-282.

[ISBN_1-58562-254-0-8] Dan J. Stein: Textbook of Anxiety Disorders. American Psychiatric Pub., 2009, ISBN 978-1-58562-900-8 , p. 196 ( limited preview in Google book search).

[pmid15388291-9] Y. Lamberty, AJ Gower: Hydroxyzine prevents isolation-induced vocalization in guinea pig pups: comparison with chlorpheniramine and immepip . In: Pharmacology, Biochemistry and Behavior . tape 79 , no. 1 , September 2004, p. 119-124 , doi : 10.1016 / j.pbb.2004.06.015 , PMID 15388291 .

[10] WS Schram: Use of hydroxyzine in psychosis. In: Dis Nerv Syst. 20, 1959, p. 126.

[pmid18504571-11] J. Kornhuber, M. Muehlbacher, S. Trapp, S. Pechmann, A. Friedl, M. Reichel, C. Mühle, L. Terfloth, T. Groemer, G. Spitzer, K. Liedl, E. Gulbins, P Tripal: Identification of novel functional inhibitors of acid sphingomyelinase . In: PLoS ONE . tape 6 , no. 8 , 2011, p. e23852 , doi : 10.1371 / journal.pone.0023852 .

[Gelbe_Liste-12] Yellow List. Retrieved July 14, 2017 .