Description
Crotamiton is an ectoparasiticide and antipruritic agent.
1,2,3 It blocks the mouse transient receptor potential vanilloid 4 (TRPV4) channel expressed in HEK293 cells in a calcium-dependent manner (IC
50s = 223.5 and 15.5 μM in buffer containing 0 and 2 mM calcium, respectively).
2 It inhibits scratching behavior in mice induced by the TRPV4 agonist GSK1016790A (Item No.
17289). Topical application of crotamiton (0.025 g of a 10% ointment) also inhibits scratching behavior in mice induced by histamine, serotonin (Item No.
14332), and the proteinase-activated receptor 2 (PAR2) agonist SLIGRL-NH
2 (Item No.
16723).
3 Formulations containing crotamiton have been used to eradicate scabies and in the treatment of symptomatic pruritic skin.
Description
Crotamiton is available as a 10% cream for the treatment of scabies, although it is less effective
than pyrethrins or permethrin. Because crotamiton may need to be applied a second time
for successful treatment of scabies but the pyrethrins or permethrin require a single application,
poor patient compliance with crotamiton may reduce its effectiveness. The advantage of crotamiton
over lindane comes from the fact that lindane has potential neurotoxicity if absorbed especially in
infants and children, whereas crotamiton has less systemic neurotoxicity.
Chemical Properties
N-Ethyl-o-crotonotoluidide is colourless or pale yellow, oily liquid
Originator
Eurax,Ciba Geigy,France,1949
Uses
N-Ethyl-o-crotonotoluidide (Crotamiton) was used to treat scabies and various pruritic dermatoses.
Uses
antipruritic, scabicide
Uses
Fungicide, insecticide.
Definition
ChEBI: The amide resulting from the formal condensation of crotonic acid with N-ethyl-2-methylaniline. A colourless or pale yellow oily liquid, it is used in the treatment of pruritus (itching) by producing a counter-irritation: as it evaporate
from the skin, it produces a cooling effect that diverts attention away from the itching. It has also been used as an acaricide in the treatment of scabies, though more effective drugs are usually preferred.
Indications
Crotamiton (N-ethyl-o-crotonotoluide, Eurax) is a synthetic chloroformate salt used
for the prevention and treatment of scabies, although cure rates tend to be lower
for the same number of applications compared with lindane and permethrin. It may
have an antipruritic effect independent of its scabetic effect. Its mechanism of action
is unknown. It is not effective as a pediculicide.
Crotamiton (10% N-ethyl-o-crotonotoluide, Eurax) cream applied twice and
left on during a 48-hour period is usually effective against scabies and has been
reported to act as an antipruritic agent.
Production Methods
The production of crotamiton involves a relatively straightforward two-step chemical synthesis. First, o-toluic acid is converted into 2-methylbenzoyl chloride using a chlorinating agent like thionyl chloride. This acyl chloride then undergoes amide formation by reacting with ethylamine, yielding N-ethyl-o-toluamide. In the second step, this intermediate is subjected to condensation with crotonic acid or crotonyl chloride, forming crotamiton.
Manufacturing Process
10.5 parts of crotonyl chloride are dropped in such a manner into 27 parts of
N-ethyl-o-toluidine, white stirring, that the temperature rises to 130° to
140°C. After cooling, the reaction product is dissolved in ether or other
solvent that is immiscible with water, and the solution is washed successively
with hydrochloric acid, alkali solution and water. After distilling off the solvent,
the residue is distilled in vacuo. The crotonic acid N-ethyl-o-toluidide boils at
153° to 155°C at a pressure of 13 mm and is a slightly yellowish oil. Instead
of carrying the reaction out in the presence of an excess of N-ethyl-otoluidine, it may be carried out in the presence of an acid-combining agent,
for example, potash, advantageously in a solvent (e.g., acetone).
Brand name
Eurax (Westwood-Squibb).
Therapeutic Function
Scabicide
Mechanism of action
Inhibits TRPV4 (transient receptor potential vanilloid 4) channel that is expressed in the skin and primary sensory neuron
Clinical Use
N-Ethyl-N-(2-methylphenyl)-2-butenamide, or N-ethyl-ocrotonotoluidide(Eurax), is a colorless, odorless oily liquid.It is virtually insoluble in water but soluble in most organicsolvents.
Crotamiton is available in 10% concentration in a lotionand a cream intended for the topical treatment of scabies. Its antipruritic effect is probably because of a local anestheticaction.
Side effects
The most common side
effect reported for crotamiton is skin irritation.
Veterinary Drugs and Treatments
Crotamiton is a topical miticide/scabicide and has been used primarily for adjunctive treatment (with ivermectin) for treating mite
infections (e.g., Knemidopkoptes) in birds. Crotamiton has both miticidal and antipruritic actions, but the mechanism for each is not
known.
References
[1] MOHAMAD GOLDUST MS Ramin R M Elham Rezaee MD. Topical ivermectin versus crotamiton cream 10% for the treatment of scabies[J]. International Journal of Dermatology, 2014, 53 7: 904-908. DOI:
10.1111/ijd.12447[2] HIROKI KITTAKA Makoto T Yu Yamanoi. Transient receptor potential vanilloid 4 (TRPV4) channel as a target of crotamiton and its bimodal effects.[J]. Pflugers Archiv?: European journal of physiology, 2017, 469 10: 1313-1323. DOI:
10.1007/s00424-017-1998-7[3] RIKA SEKINE. Anti pruritic effects of topical crotamiton, capsaicin, and a corticosteroid on pruritogen-induced scratching behavior[J]. Experimental Dermatology, 2011, 21 3: 201-204. DOI:
10.1111/j.1600-0625.2011.01433.x
Pesticide Type
Insecticide; Acaricide; Veterinary substance
