Promethazine
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| Non-proprietary name | Promethazine | ||||||||||||
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190-192 ° C (400 Pa) |
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0.18 m Pa (25 ° C) |
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| pK s value |
9.1 |
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Promethazine is an active ingredient from the phenothiazine group that, unlike other substances in this class, is not used as an antipsychotic . Promethazine is instead used as a sedative ( sedative ), and in particular indications as antihistamine and antiemetic application. Promethazine was developed by the same researchers who shortly later synthesized the first neuroleptic ( chlorpromazine ).
Mode of action
The messenger substance histamine regulates various functions in the brain and also triggers those complaints that occur with an allergy. Promethazine occupies the histamine binding sites in the brain. It has a calming and sleep-inducing effect. In addition, promethazine also binds to the muscarinic acetylcholine receptor and to the receptors for 5-HT2A , 5-HT2C , dopamine-D2 , the NMDA - glutamate receptor and the α1-adrenoreceptor . Promethazine is also a potent antioxidant and increases glutamate uptake in glial cells in the brain.
The neuroleptic potency of promethazine is given in the literature as 0.5. It is therefore considered to be a low-potency neuroleptic with a primarily sedative effect. In Germany, promethazine is only used in exceptional cases to treat allergic symptoms if simultaneous sedation of the patient is desired ("psychoantiallergic").
Promethazine also acts as a FIASMA (functional inhibitor of acid sphingomyelinase ).
Pharmacokinetics
Promethazine is quickly and almost completely absorbed from the intestinal lumen, but is subject to a very pronounced first-pass effect (metabolism during the first liver passage directly after being absorbed into the blood), which results in a low bioavailability . The maximum blood plasma concentrations are measured 1.5 to 3 hours after administration, the plasma half-life is 10 to 12 hours. The metabolism (breakdown) takes place via CYP2D6, an enzyme from the cytochrome P450 group. The metabolites (degradation products) are pharmacologically inactive, so they have no effects of their own.
application areas
- Restlessness and agitation in the context of underlying psychiatric diseases
- Acute allergic reactions of the immediate type when sedation is indicated at the same time (intravenous use)
- Nausea and vomiting (orally, when therapeutic alternatives are not feasible or have not been successful)
- Sleep disorders in adults (oral when therapeutic alternatives are impractical or unsuccessful)
- Anxiety disorders
unwanted effects
Among the side effects dry mouth include difficulty focusing of the eye , constipation , micturition disorders , negative effects on libido and sexual performance and other vegetative disorders. Impairment of nasal breathing is possible. In rare cases and in the event of an overdose, hallucinations, confusion and severe motor impairment (including restless legs syndrome ) can occur.
Interactions
The depressant effects of alcohol, sleeping pills and painkillers as well as other drugs that have an effect on the psyche are intensified when used at the same time as promethazine.
Promethazine can increase the effects of antihypertensive drugs.
Dosage forms
Promethazine comes in the form of tablets , oral drops, and a solution for injection .
In Switzerland, Phenergan, used as an antihistamine with the active ingredient promethazine, was withdrawn from the market on January 31, 2009, while Phenergan continues to be sold in France.
In Spain, promethazine is approved as an effective component of a topical ointment (trade name: Fenergán ) for the treatment of insect bites from blood-sucking insects.
A 2% ointment for the treatment of insect bites, skin irritations and sunburns is also available without a prescription in Italy under the trade name Reactifargan .
In Sweden, promethazine is approved as Lergigan and as a combination preparation with ephedrine and caffeine ( Lergigan comp ) for the treatment of anxiety disorders, sleep disorders, kinetoses , postoperative nausea and vomiting, Menière's disease and allergies.
synthesis
The synthesis is carried out by nucleophilic substitution starting from phenothiazine and ( RS ) -2-chloro- N , N- dimethyl-1-propylamine .
In this synthesis, the drug is created as a racemate .
Stereoisomerism
Promethazine is chiral and contains a stereocenter, so there are two enantiomers , the ( R ) form and the ( S ) form. The commercial preparations contain the drug as a racemate (1: 1 mixture of enantiomers).
Trade names
Atosil (D), Phenergan (USA), Closin (D), Farganesse (I), Proneurin (D), Prothazine (D), Promethazin-neuraxpharm (D), Allersoothe (NZ)
See also
Individual evidence
- ↑ a b c d e Entry on promethazine in the ChemIDplus database of the United States National Library of Medicine (NLM)
- ↑ a b The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition. 2006, ISBN 0-911910-00-X , p. 1339.
- ^ Entry on promethazine. In: Römpp Online . Georg Thieme Verlag, accessed on May 29, 2014.
- ↑ a b Data sheet Promethazine hydrochloride from Sigma-Aldrich , accessed on April 22, 2011 ( PDF ).
- ↑ a b Antiemetic therapy for vomiting. In: Medicinal Telegram . 40, 2009, pp. 87-89.
- ^ Bangen, Hans: History of the drug therapy of schizophrenia. Berlin 1992, The synthesis of chlorpromazine pp. 73-80 ISBN 3-927408-82-4
- ↑ D. Fiorella, RA Rabin, JC Winter: The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs. I: Antagonist correlation analysis. In: Psychopharmacology. 121 (3), October 1995, pp. 347-356. PMID 8584617
- ↑ P. Seeman, M. Watanabe, D. Grigoriadis et al: Dopamine D2 receptor binding sites for agonists. A tetrahedral model. In: Molecular Pharmacology . 28 (5), November 1985, pp. 391-399. PMID 2932631
- ↑ DR Burt, I. Creese, SH Snyder: Antischizophrenic drugs: chronic treatment elevates dopamine receptor binding in brain. In: Science. 196 (4287), April 1977, pp. 326-328. doi: 10.1126 / science.847477 . PMID 847477
- ^ P. Jagadish Prasad: Conceptual Pharmacology. Universities Press, 2010, ISBN 978-81-7371-679-9 , pp. 295, 303, 598.
- ↑ O. Adolph et al: Promethazine inhibits NMDA-induced currents - new pharmacological aspects of an old drug. In: Neuropharmacology . 63 (2), Aug 2012, pp. 280-291. doi: 10.1016 / j.neuropharm.2012.03.006 . Epub 2012 Apr 7.
- ↑ P. Buc-Calderon, I. Latour, M. Roberfroid: Biochemical changes in isolated hepatocytes exposed to tert-butyl hydroperoxide. Implications for its cytotoxicity. In: Cell Biol Toxicol . 7 (2), Apr 1991, pp. 129-143.
- ↑ VV Binder, KJ Föhr, O. Adolph, M. Georgieff: PO-4.1.11 Promethazine (Atosil) increases the glutamate uptake in glial cells - possible importance for pain therapy. Ulm University Hospital.
- ↑ H.-J. Möller, WE Müller, B. Bandelow: Neuroleptics - Pharmacological basics, clinical knowledge and therapeutic approach. Scientific publishing company, Stuttgart 2001.
- ↑ Drug database "Drug Telegram": Promethazine. ( Memento of the original from April 14, 2016 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Retrieved October 18, 2013.
- ↑ 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 .
- ↑ Otto Benkert, Hanns Hippius: Compendium of Psychiatric Pharmacotherapy. 8th edition. Springer, 2011, ISBN 978-3-642-13043-4 .
- ↑ Atosil drops , last seen on September 30, 2017.
- ↑ Entry on Rhinathiol Promethazin in Pharmawiki , accessed on January 28, 2017.
- ^ Axel Kleemann , Jürgen Engel, Bernd Kutscher, Dietmar Reichert: Pharmaceutical Substances. 4th edition. 2 volumes. Thieme-Verlag, Stuttgart 2000, ISBN 1-58890-031-2 . (online since 2003 with biannual additions and updates).
