Cloperastine

Cloperastine (INN) or cloperastin, in the forms of cloperastine hydrochloride (JAN) (brand names Hustazol, Nitossil, Seki) and cloperastine fendizoate, is an antitussive and antihistamine that is marketed as a cough suppressant in Japan, Hong Kong, Brazil and in some European countries.^[1][2][3] It was first introduced in 1972 in Japan, and then in Italy in 1981.^[4]

Cloperastine

Cloperastine structure (above); (S)-cloperastine 3D molecule (below)
Clinical data
Other names	HT-11
AHFS/Drugs.com	International Drug Names
Routes of administration	Oral
ATC code	R05DB21 (WHO)
Identifiers
IUPAC name 1-[2-[(4-Chlorophenyl)-phenyl-methoxy]ethyl]piperidine
CAS Number	3703-76-2 Y
PubChem CID	2805
DrugBank	DB09002 N
ChemSpider	2703 Y
UNII	69M5L7BXEK
KEGG	D03557 Y
ChEMBL	ChEMBL415087 Y
CompTox Dashboard (EPA)	DTXSID7048532
ECHA InfoCard	100.020.948
Chemical and physical data
Formula	C20H24ClNO
Molar mass	329.87 g·mol−1
3D model (JSmol)	Interactive image
SMILES Clc1ccc(cc1)C(OCCN2CCCCC2)c3ccccc3
InChI InChI=1S/C20H24ClNO/c21-19-11-9-18(10-12-19)20(17-7-3-1-4-8-17)23-16-15-22-13-5-2-6-14-22/h1,3-4,7-12,20H,2,5-6,13-16H2 Y Key:FLNXBVJLPJNOSI-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Side effects

Adverse effects may include sedation, drowsiness, heartburn, and thickening of bronchial secretions.^[5]

Pharmacology

The precise mechanism of action of cloperastine is not fully clear, but several different biological activities have been identified for the drug, of which include: ligand of the σ₁ receptor (K_i = 20 nM) (likely an agonist),^[6] GIRK channel blocker (described as "potent"),^{[7][8][9][10]} antihistamine (K_i = 3.8 nM for the H₁ receptor),^[3][6] and anticholinergic.^[3][11] It is thought that the latter two properties contribute to side effects, such as sedation and somnolence, while the former two may be involved in or responsible for the antitussive efficacy of cloperastine.^[6][7]

Synthesis

Synthesis:^[12] Patents:^[13][14] Isomers:^[15] China:^[16]

The halogenation of 4-Chlorobenzhydrol [119-56-2] (1) with phosphorus tribromide in tetrachloromethane gives 1-(Bromophenylmethyl)-4-chlorobenzene [948-54-9] (2). Treatment with ethylenechlorohydrin (2-Chloroethanol) [107-07-3] (3) gives 1-(4-Chlorobenzhydryl)oxy-2-chloroethane [5321-46-0] (4). Reaction with piperidine (5) completes the synthesis of Cloperastine (6).

See also

• Cough syrup
• Noscapine
• Codeine; Pholcodine
• Dextromethorphan; Dimemorfan
• Racemorphan; Dextrorphan; Levorphanol
• Butamirate
• Pentoxyverine
• Tipepidine
• Levocloperastine