Salmeterol

Salmeterol Properties

Melting point	75.5-76.5°
Boiling point	603.0±55.0 °C(Predicted)
Density	1.112±0.06 g/cm3(Predicted)
storage temp.	2-8°C
solubility	Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
pka	9.99±0.31(Predicted)
form	Solid
color	White to Off-White
CAS DataBase Reference	89365-50-4(CAS DataBase Reference)

SAFETY

Risk and Safety Statements

Symbol(GHS)	GHS07
Signal word	Warning
Hazard statements	H315-H319-H335
Precautionary statements	P261-P305+P351+P338
RTECS	CZ6457000

Salmeterol Chemical Properties,Uses,Production

Uses

Salmeterol is a β2-Adrenergic agonist used for relief and control of asthma symptoms.

Definition

ChEBI: A phenol having a hydroxymethyl group at C-2 and a 1-hydroxy-2-{[6-(4-phenylbutoxy)hexyl]amino}ethyl group at C-4; derivative of phenylethanolamine.

General Description

Salmeterol has an N-phenylbutoxyhexyl substituent incombination with a β-OH group and a salicyl phenyl ring foroptimal direct-acting β2-receptor selectivity and potency. Ithas a potency similar to that of ISO. This drug associateswith the β2-receptor slowly resulting in slow onset of actionand dissociates from the receptor at an even slower rate. It is resistant to both MAO and COMT and highly lipophilic(log P=3.88). It is thus very long acting (12 hours), aneffect also attributed to the highly lipophilic phenylalkylsubstituent on the nitrogen atom, which is believed to interactwith a site outside but adjacent to the active site.
Salmeterol

Hazard

A poison by inhalation.

Biological Activity

Potent and selective β 2 -adrenoceptor agonist (EC 50 = 5.3 nM); bronchodilator. Unlike other β 2 agonists, binds to exo-site domain of β 2 receptors, producing a slow onset of action and prolonged activation. Also available as part of the β -Adrenoceptor Agonist Tocriset™ .

Mechanism of action

A β2-agonist with a slow onset and extended duration of action is salmeterol. Salmeterol has the same phenyl ring substitution R3 as albuterol but also an unusually long and lipophilic group R1 on the nitrogen. The octanol–water partition coefficient, log P, for salmeterol is 3.88, compared with 0.66 for albuterol. Salmeterol is approximately 50-fold more selective than albuterol for the β2-receptor. Substantial evidence indicates that its long duration of action results from a specific binding interaction (“anchoring”) of the phenyl group at the end of the extended lipophilic side chain with a specific region of the β2-receptor, affording salmeterol a unique binding mechanism.

Pharmacokinetics

Salmeterol is 94 to 98% bound to human plasma proteins, both albumin and α1-acid glycoprotein, in vitro over the concentration range of 8 to 7722μg of base/L, much higher concentrations than those achieved following therapeutic doses of this drug. When salmeterol is inhaled, plasma concentrations of the drug often cannot be detected, even 30 minutes after administration of therapeutic doses. Larger inhaled doses give approximately proportionally increased blood concentrations. Plasma salmeterol concentrations of 0.1 to 0.2 and 1 to 2 μg/L were attained in healthy volunteers about 5 to 15 minutes after inhalation of single doses of 50 and 400μg, respectively. These concentrations were most probably related to the drug passing rapidly through the alveolar-capillary interface and probably into mucosal and submucosal vessels. In patients who inhaled salmeterol 50μg twice a day for 10 months, a second Cmax of 0.07 to 0.2 μg/L occurred 45 to 90 minutes after inhalation, probably due to gastrointestinal absorption of the swallowed drug (most of the dose delivered by a metered-dose inhaler is swallowed). Oral administration of 1mg of radiolabelled [14C]salmeterol (as salmeterol xinafoate) to two healthy individuals gave peak plasma salmeterol concentrations of about 650 μg/L at about 45 minutes. In another volunteer, t1 ?2β was about 5.5 hours. The dose-normalised Cmax values in comparative animal studies suggest that the systemic absorption and bioavailability in humans is greater (about 15 times greater) than that in rodents, being more closely related to that in dogs. Absorption may be high in humans, and first-pass metabolism less than in animals[1].

Clinical Use

Salmeterol usually is prescribed for severe persistent asthma following previous treatment with a short-acting β-agonist, such as albuterol. The noticeable differences between salmeterol and albuterol are the onset of action and their duration of action (Table 13.6). When used regularly every day as prescribed, inhaled albuterol decreases the number and severity of asthma attacks. It is not used, however, for relieving an asthma attack that has already started.

Side effects

Hoarseness, throat irritation, headache, rapid heartbeat, nervousness, cough, dry mouth/throat, or upset stomach may occur. To relieve dry mouth, suck on (sugarless) hard candy or ice chips, chew (sugarless) gum, drink water, or use a saliva substitute. This medication may raise your blood pressure. Rarely, this medication may cause sudden breathing problems/asthma right after you use it. If this occurs, use your quick-relief inhaler and get medical help right away.

Drug interactions

Many drugs besides salmeterol may affect the heart rhythm (QT prolongation), including amiodarone, dofetilide, pimozide, procainamide, quinidine, sotalol, macrolide antibiotics (such as erythromycin), among others. Before using salmeterol, report all medications you are currently using to your doctor or pharmacist.Other medications can affect the removal of salmeterol from your body, which may affect how salmeterol works. Examples include cobicistat, nefazodone, ritonavir, telithromycin, azole antifungals (such as ketoconazole, itraconazole), macrolide antibiotics (such as clarithromycin), HIV protease inhibitors (such as saquinavir), among others.

Metabolism

Salmeterol is metabolized predominantly through CYP3A4, an isoform of cytochrome P450. CYP3A4 is responsible for the aliphatic oxidation of the salmeterol base. Salmeterol is extensively metabolized by hydroxylation into alpha-hydroxy-salmeterol and subsequently eliminated through feces and urine. Salmeterol is 57.4% eliminated in the feces and 23% in the urine. At recommended doses, systemic concentrations of salmeterol are low or undetectable. Only at very high doses are blood concentrations increased.

References

[1] M. Cazzola, M. Matera, R. Testi. “Clinical Pharmacokinetics of Salmeterol.” Clinical Pharmacokinetics 41 1 (2002): 19–30.

Salmeterol Preparation Products And Raw materials

Raw materials

N, O-DIBENZYL SALMETEROL 4-Hydroxy-alpha1-[[[6-(4-phenylbutoxy)hexyl](phenylmethyl)amino]methyl]-1,3-benzenedimethanol

Preparation Products

Salmeterol Suppliers

Global( 190)Suppliers

Supplier	Tel	Country	ProdList	Advantage	Inquiry
J S LABS	+91-7330612784 +91-7330612784	Tamil Nadu, India	160	58	Inquiry
A.J Chemicals	91-9810153283	New Delhi, India	6124	58	Inquiry
CLEARSYNTH LABS LTD.	+91-22-45045900	Hyderabad, India	6351	58	Inquiry
Parth Antibiotics Pvt Ltd.	+91 (22) 2562-8329	New Delhi, India	173	50	Inquiry
Triveni chemicals	08048762458	New Delhi, India	6093	58	Inquiry
Pharmaffiliates Analytics and Synthetics P. Ltd	+91-172-5066494	Haryana, India	6773	58	Inquiry
BIONNA MEDICINE CO.,LTD	01056380788-8515; +8618518759099	China	52	58	Inquiry
Zibo Hangyu Biotechnology Development Co., Ltd	+86-0533-2185556 +8617865335152	China	10991	58	Inquiry
Henan Tianfu Chemical Co.,Ltd.	+86-0371-55170693 +86-19937530512	China	21667	55	Inquiry
Hangzhou FandaChem Co.,Ltd.	008657128800458; +8615858145714	China	9355	55	Inquiry

Supplier	Advantage
J S LABS	58
A.J Chemicals	58
CLEARSYNTH LABS LTD.	58
Parth Antibiotics Pvt Ltd.	50
Triveni chemicals	58
Pharmaffiliates Analytics and Synthetics P. Ltd	58
BIONNA MEDICINE CO.,LTD	58
Zibo Hangyu Biotechnology Development Co., Ltd	58
Henan Tianfu Chemical Co.,Ltd.	55
Hangzhou FandaChem Co.,Ltd.	55

89365-50-4(Salmeterol)Related Search:

3,4'-DIAMINODIPHENYLMETHANE Tris(hydroxymethyl)nitromethane Ethyl acetate SALMETEROL XINAFOATE,SALMETEROL XINAFONATE,Salmeterol, 1-Hydroxy-2-naphthoate Acetaminophen

Ethyl cellulose 2-Phenylphenol 3-Aminophenol Ethyl acrylate CHLOROPHOSPHONAZO III

Ethanol Ethylparaben 4-Aminophenol 2-Aminophenol SALMETEROL-D3,SALMETEROL-D3 (3-HYDROXYMETHYL-D2, ALPHA-D1)

Benzoic acid, 3-acetyl-4-(phenylmethoxy)-, methyl ester SalMeterol EP IMpurity F 3-Bromo-benzenebutanol

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4-HYDROXY-A1-[[[6-(4-PHENYLBUTOXY)HEXYL]AMINO]METHYL]-1,3-BENZENEDIMETHANOL 2-(hydroxymethyl)-4-[1-hydroxy-2-[6-(4-phenylbutoxy)hexylamino] ethyl]-phenol SALMETEROL (+-)-4-hydroxy-alpha1-(((6-(4-phenylbutoxy)hexyl)amino)methyl)-1,3-benzenedi 1,3-benzenedimethanol,4-hydroxy-alpha1-(((6-(4-phenylbutoxy)hexyl)amino)methyl gr33343x SALMETEROL(SUBJECTTOPATENTFREE) SAMETEROL 1,3-Benzenedimethanol, 4-hydroxy-a1-[[[6-(4-phenylbutoxy)hexyl]amino]methyl]- (9CI) 1,3-Benzenedimethanol, 4-hydroxy-a1-[[[6-(4-phenylbutoxy)hexyl]amino]methyl]-, (+-)- GR 33343, 4-Hydroxy-a1-[[[6-(4-phenylbutoxy)hexyl]amino]m-ethyl]-1,3-benzenedimethanol SalmeterolXenofoate 4-Hydroxy-3-[hydroxymethyl]phenyl-N-[6-phenylbutoxyhexyl]ethanolamine Salmeterol & Salmeterol Xinafoate 4-Hydroxy-α1-[[[6-(4-phenylbutoxy)hexyl]amino]methyl]-1,3-benzenedimethanol 4-[(1R)-1-hydroxy-2-{[6-(4-phenylbutoxy)hexyl]aMino}ethyl]-2-(hydroxyMethyl)phenol salmeterol Solution, 100ppm GR 33343 Salmeterol, >=99% BNKY006-SX05 CS-380 Astmerole SN408D [(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl]-[6-(4-phenylbutoxy)hexyl]ammonium 1,3-Benzenedimethanol, 4-hydroxy-α1-[[[6-(4-phenylbutoxy)hexyl]amino]methyl]- Salmeterol USP/EP/BP Salmeterol Xenofoate USP (RS)-2-(hydroxymethyl)-4-{1-hydroxy-2-[6-(4-phenylbutoxy)hexylamino]ethyl}phenol (API) Salmeterol base 89365-50-4 C25H34NO4D3 C25H37NO4 API Aromatic Building Blocks