Hazard
Headache, flushing, gastrointestinal distress, diarrhea, hypotension, excessive salivation, sweating, hypersensitivity.
Description
Bethanechol is an agonist of muscarinic acetylcholine receptors with IC
50 values of 1,837, 25, 631, 317, and 393 μM for M
1-5, respectively, in a radioligand binding assay using CHO cells expressing the human receptors.
1 It inhibits M
2-mediated increases in cyclic AMP induced by isoproterenol (Item No.
15592) in isolated guinea pig small intestine (IC
50 = 127 μM).
2 Bethanechol increases basal tone of isolated porcine intravesical ureter (EC
50 = 4.27 μM).
3 It also induces fluid secretion in the ileum, duodenum, and jejunum of anesthetized rats when administered at a dose of 60 μg/kg.
4 Formulations containing bethanechol have been used to increase urination and improve smooth muscle tone in the gastrointestinal tract.
Chemical Properties
White Solid
Originator
Urecholine CI,MSD,US,1949
Uses
A selective muscarinic receptor stimulant, used to treat cerebral palsy.
Uses
Therapeutic action of Betanechol is based on this action, and it is used for treating postoperational non-obstructive retention of urine and neurogenic bladder atony. Earlier, it was
used for treating gastrointestinal illnesses and Alzheimer’s disease.
Definition
ChEBI: The chloride salt of bethanechol. A slowly hydrolysed muscarinic agonist with no nicotinic effects, it is used to increase smooth muscle tone, as in the gastrointestinal tract following abdominal surgery, treatment of gastro-oesophageal reflux disease, and
as an alternative to catheterisation in the treatment of non-obstructive urinary retention.
Manufacturing Process
About 3 grams of β-methylcholine chloride are stirred at room temperature
with an excess of phosgene dissolved in 50 grams of chloroform, for about 2
hours. Excess phosgene and hydrochloric acid are removed by distillation
under vacuo. Additional chloroform is added to the syrup and the mixture is
poured into excess ammonia dissolved in chloroform and cooled in solid
carbon dioxide-acetone. The solid is filtered and extracted with hot absolute
alcohol. The solid in the alcohol is precipitated with ether, filtered, and
recrystallized from isopropanol. The carbaminoyl-β-methylcholine chloride
obtained has a melting point of about 220°C.
Brand name
Duvoid (WellSpring); Myotonachol (Glenwood);
Urecholine (Odyssey).
Therapeutic Function
Cholinergic
General Description
Bethanechol, β-methylcholinechloride carbamate, (2-hydroxypropyl)trimethylammoniumchloride carbamate, carbamylmethylcholinechloride (Urecholine), is nonspecific in its action on muscarinicreceptor subtypes but appears to be more effective ateliciting pharmacological action of M3 receptors. It haspharmacological properties similar to those of methacholine.Both are esters of β-methylcholine and have feeblenicotinic activity. Bethanechol is inactivated more slowlyby AChE in vivo than is methacholine. It is a carbamyl esterand is expected to have stability in aqueous solutions similarto that of carbachol.
Mechanism of action
Bentanechol is a drug, which has structurally unique qualities of both methacholine and
carbachol, i.e. it contains both β-methyl and carbamate functional groups, and quite
logically exhibits pharmacological properties of both the drugs. It is resistant to hydrolysis by cholinesterases and has a very minor effect on nicotinic receptors of the
autonomic ganglia and neuromuscular junctions. Betanechol has more of a selective
action on muscarinic receptors of the gastrointestinal tract and the bladder than do other
cholinic esters.
Clinical Use
The main use of bethanechol chloride is in the relief ofurinary retention and abdominal distention after surgery.The drug is used orally and by subcutaneous injection. Itmust never be administered by intramuscular or intravenousinjection because of the danger from cholinergic overstimulationand loss of selective action. Proper administration ofthe drug is associated with low toxicity and no serious sideeffects. Bethanechol chloride should be used with caution inasthmatic patients; when used for glaucoma, it producesfrontal headaches from the constriction of the sphinctermuscle in the eye and from ciliary muscle spasms. Its durationof action is 1 hour.
Synthesis
Betanechol, 2-carbamoyloxy-1-(N,N,N-trimethyl)propyl ammonium chloride (13.1.8), is made by either the subsequent reaction of 1-(N,N,N-trimethylammonium)
propan-2-ol with phosgene, followed by ammonia, or by a completely analogous
synthesis of carbachol by the reaction of 1-chloro-2-propanol with phosgene followed by
consequent reactions with ammonia, and then with trimethylamine, giving betanechol
(13.1.8) [14,15].
Veterinary Drugs and Treatments
In veterinary medicine, bethanechol is used primarily to stimulate
bladder contractions
in small animals. It also can be used as an
esophageal or general GI stimulant, although metoclopramide
and/
or neostigmine have largely supplanted it for these uses.
References
[1] M H RICHARDS P L van G. Human muscarinic receptors expressed in A9L and CHO cells: activation by full and partial agonists.[J]. British Journal of Pharmacology, 1995, 114 6: 1241-1249. DOI:
10.1111/j.1476-5381.1995.tb13339.x[2] H OKAMOTO. Muscarinic agonist potencies at three different effector systems linked to the M2 or M3 receptor in longitudinal smooth muscle of guinea-pig small intestine[J]. British Journal of Pharmacology, 2009, 135 7: 1765-1775. DOI:
10.1038/sj.bjp.0704642[3] M. HERNáNDEZ. Different muscarinic receptor subtypes mediating the phasic activity and basal tone of pig isolated intravesical ureter[J]. British Journal of Pharmacology, 1993, 110 4: 1413-1420. DOI:
10.1111/j.1476-5381.1993.tb13978.x[4] A YOUNG R J L. Intestinal hypersecretion of the refed starved rat: a model for alimentary diarrhoea.[J]. Gut, 1992, 33 8: 1050-1056. DOI:
10.1136/gut.33.8.1050
