Originator
Bentyl ,Merrell National ,US,1950
Definition
ChEBI: The ester resulting from the formal condensation of 1-cyclohexylcyclohexanecarboxylic acid with 2-(diethylamino)ethanol. An anticholinergic, it is used as the hydrochloride to treat or prevent spasm in the muscles of the gastrointestinal tract, particularl
that associated with irritable bowel syndrome.
Manufacturing Process
155 grams of 1-phenylcyclohexanecyanide, 350 cc of concentrated sulfuric
acid and 1,130 cc of ethyl alcohol are refluxed vigorously for 48 hours. The
remaining alcohol is then removed by vacuum distillation and the residue is
poured into 1 liter of ice water. An oil separates which is extracted 3 times
with 200 cc portions of petroleum ether, the extracts are combined and heated on a steam bath to remove the ether. The resulting crude ester may
be used directly for the reesterification operation or it may be distilled to
purify it first. A mixture of the ester so obtained, 155 grams of βdiethylaminoethanol and 800 cc of dry xylene are placed in a reaction vessel
with about 2 grams of sodium. The vessel is heated in an oil bath at 150°-
160°C. A xylene-ethanol azeotrope distills over at about 78°-82°C over a
period of 2 to 3 hours. The distillate is cooled and shaken with about 3 times
its volume of water, the decrease in volume of the distillate being considered a
measure of the amount of alcohol formed. When 80-90% of the theoretical
amount of alcohol is obtained in the distillate the reaction mixture is subjected
to vacuum distillation to remove most of the xylene and unreacted
diethylaminoethanol. The residue is poured into 500 cc of benzene which is
then extracted 3 times with 500 cc portions of water.
The washed benzene layer is diluted with an equal volume of ether and
alcoholic hydrochloric acid is added until the mixture is acid to Congo red. A
white crystalline solid forms which is dissolved in 300-400 cc of alcohol and
diluted with ether to the point where precipitation starts. A few drops of
butanone are added, the solution is cooled to -10°C, and filtered to recover
the crystals which separate. The product is obtained in the form of white
needles melting at 159°-160°C, in good yield.
13 parts of β-diethylaminoethyl 1-phenylcyclohexanecarboxylate
hydrochloride, 125 parts of glacial acetic acid and 0.3 part of Adams' catalyst
are heated to 70°C and shaken with hydrogen at 50 lb pressure until 90-
100% of the theoretical hydrogen is absorbed. The acetic acid is then
removed by distillation and the residue recrystallized from butanone, giving
the above product as a crystalline hydrochloride melting at 165°-166°C, in
good yields. This product may also be prepared by reacting cyclohexyl
bromide with cyclohexyl cyanide with the use of sodium amide followed by
alcoholysis and reesterification.
brand name
Bentyl (Axcan Scandipharm);Abacid plus;Ametil;Babypasmil;Babyspasmil;Baycyclomine;Benacol;Colix;Cyclobex;Cyclocen;Diarrest;Diclophen;Eatongel;Esentil;Fomulex;Formulex;Gastrosilane;Icramin;Incramin;Incron;Inctacol-c;Isospamex;Kolanticon;Lagasediv;Menospasm;Merbantal;Neoquess;Nomocramp;Notensyl;Or-tyl;Pamin;Panakiron;Prinel;Protylol;Sawamin;Spactil;Spasmoban;Spastil;Tarestin;Viscerol.
Therapeutic Function
Spasmolytic
World Health Organization (WHO)
Dicycloverine, an anticholinergic agent with antispasmodic and
local anaesthetic activity, was introduced in 1952 for treatment of functional
conditions involving smooth muscle of the gastrointestinal tract. Its use in the
treatment of colic in infants under six months of age has been associated with
irritability and restlessness, convulsions and apnoea which has led the major
manufacturer to issue revised global prescribing information in 1985
contraindicating the use of dicycloverine in this age group. Subsequently
restrictive regulatory action directed to other available brands of this drug was taken in several countries. Preparations containing dicycloverine remain available
in at least ten major markets.
