Tulobuterol

Structural formula
1: 1 mixture of ( R ) -form (top) and ( S ) -form (bottom)
General
Non-proprietary name	Tulobuterol
other names	( RS ) -2-tert-butylamino-1- (2-chlorophenyl) ethanol rac -2-tert-butylamino-1- (2-chlorophenyl) ethanol DL -2-tert-butylamino-1- (2-chlorophenyl) ethanol
Molecular formula	C 12 H 18 ClNO
Brief description	crystalline
External identifiers / databases
CAS number 41570-61-0 (tulobuterol) 56776-01-3 (tulobuterol hydrochloride ) EC number 640-961-9 ECHA InfoCard 100.168.691 PubChem 5606 ChemSpider 5404 DrugBank DB12248 Wikidata Q909353
Drug information
ATC code	R03 CC11
Drug class	Bronchodilator (β 2 sympathomimetic)
properties
Molar mass	227.73 g · mol -1
Melting point	89-91 ° C (tulobuterol) 161–163 ° C (tulobuterol hydrochloride )
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances Hydrochloride Caution H and P phrases H: 302 P: no P-phrases
Toxicological data	305 mg kg −1 ( LD 50 , male mouse ,  oral ) 850 mg kg −1 ( LD 50 ,  rat ,  oral ) 563 mg kg −1 ( LD 50 ,  rabbit ,  oral )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Tulobuterol (trade name: Brelomax ^® manufacturer: Abbott Laboratories ) is a drug used in the treatment and prevention of shortness of breath in bronchial asthma , chronic obstructive bronchitis and bronchopulmonary diseases with bronchospastic conditions.

Clinical information

Application areas (indications)

Tulobuterol is approved for the prevention and treatment of respiratory diseases that are associated with narrowing of the airways due to spasms of the bronchial muscles (obstructive airway diseases).

Type and duration of application

Tulobuterol is on the market in Germany in the form of a syrup for oral administration. Oral dosage forms should only be used if targeted topical administration of another β ₂ -sympathomimetic is not possible. In the case of long-term administration, anti-inflammatory co-medication should be used.

Contraindications (contraindications)

Tulobuterol must not be used if there is a known hypersensitivity to this active ingredient. A recent heart attack and tachycardias with and without arrhythmias are also contraindications.

Drug interactions

Due to the potassium level-lowering effect of tulobuterol, an increased effect of cardiac glycosides can occur.

Use during pregnancy and breastfeeding

There are insufficient data on use during pregnancy and breastfeeding. It can be assumed that tulobuterol passes into breast milk.

Adverse effects (side effects)

Side effects observed particularly affect the cardiovascular system , the nervous system , the gastrointestinal tract , the blood sugar and electrolyte balance and the skeletal muscles . The most common are tremors , nausea , headache , dizziness, and palpitations . These side effects are at least partially reversible.

During therapy with tulobuterol, as with therapy with other beta-sympathomimetics, cardiovascular side effects such as lowering or increasing blood pressure , palpitations, tachycardia, arrhythmias and angina pectoris can occur. Gastrointestinal side effects include stomach discomfort and vomiting. Tulobuterol can cause a decrease in the level of potassium in the blood ( hypokalaemia ) and an increase in the level of sugar in the blood ( hyperglycaemia ). Furthermore, hypersensitivity reactions, headache, nervousness, sweating, dizziness, nausea, tremor, hyperactivity, sleep disorders, hallucinations, muscle pain and muscle cramps can occur.

Pharmacological properties

Mechanism of action (pharmacodynamics)

Tulobuterol is a drug from the group of β ₂ sympathomimetics . By stimulating β ₂ -adrenoceptors , tulobuterol relaxes the smooth muscles and thus dilates the airways. At the same time, however, tulobuterol leads to an expansion of the blood vessels and thus a reflex increase in the heart rate .

Absorption and distribution in the body (pharmacokinetics)

After oral administration, tulobuterol is almost completely absorbed from the small intestine and is partially bound to plasma proteins in the blood (approx. 30%). Most of the metabolism of tulobuterol takes place in the liver . Tulobuterol and its metabolic products ( metabolites ) are mainly excreted via the kidneys. Its plasma half-life is about three hours, that of its active metabolites nine to twelve hours.

chemistry

Stereochemistry

Tulobuterol contains a stereocenter , so it is chiral . Thus there are two isomers, the ( R ) form and the ( S ) form. The commercial preparations contain a tulobuterol hydrochloride as a racemate [1: 1 mixture of the ( R ) and the ( S ) stereoisomer].

synthesis

The three-step synthesis of racemic tulobuterol is based on 2'-chloroacetophenone . The oxidation product 2-chlorophenylglyoal is reacted with tert- butylamine to form the imine . The keto group and the imine function are then reduced with sodium borohydride .

Synthesis of tulobuterol

Individual evidence

1. ↑ ^{a b c d e f} The Merck Index. An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, p. 1685, ISBN 978-0-911910-00-1 .
2. ↑ ^{a b} Datasheet Tulobuterol hydrochloride from Sigma-Aldrich , accessed on May 19, 2017 ( PDF ).
3. ↑ ^{a b c d e} Specialist information Brelomax syrup. Abbott GmbH & Co. KG. April 2008.
4. ^ Axel Kleemann , Jürgen Engel, Bernd Kutscher and Dieter Reichert: Pharmaceutical Substances, 4th Edition (2000) 2 volumes published by Thieme-Verlag Stuttgart, pp. 2142-2143, ISBN 978-1-58890-031-9 ; online since 2003 with biannual additions and updates.

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !