Homatropine methylbromide
[CAS# 80-49-9]

Identification

• Classification: API >> Nervous system medication >> Cholinergic
• Name: Homatropine methylbromide
• Synonyms: [(1S,5R)-8,8-dimethyl-8-azoniabicyclo[3.2.1]octan-3-yl] 2-hydroxy-2-phenylacetate bromide
• Molecular Formula: C₁₆H₂₁NO₃^.CH₃Br
• Molecular Weight: 370.28
• CAS Registry Number: 80-49-9
• EC Number: 201-284-0
• SMILES: C[N+]1([C@@H]2CC[C@H]1CC(C2)OC(=O)C(C3=CC=CC=C3)O)C.[Br-]

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302
• Precautionary Statements: P264-P270-P301+P317-P330-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H332

Discovory and Applicatios

Homatropine methylbromide is a quaternary ammonium compound classified as a muscarinic acetylcholine receptor antagonist. Its molecular formula is C₁₆H₂₂NO₃Br, and it is chemically related to atropine and homatropine, differing by the presence of a methyl group on the nitrogen, forming a permanent positive charge (quaternary ammonium) and a bromide counterion. This structure restricts its ability to cross the blood-brain barrier, thereby limiting central nervous system effects.

The compound was developed in the early 20th century during the investigation of atropine derivatives for therapeutic use. Homatropine itself was synthesized as a semi-synthetic alkaloid derived from tropine and mandelic acid. Homatropine methylbromide results from the methylation of homatropine, forming a bromide salt that is more water-soluble and exhibits different pharmacological properties.

Homatropine methylbromide is primarily used for its anticholinergic effects on smooth muscles in the gastrointestinal, biliary, and genitourinary systems. As a muscarinic receptor antagonist, it inhibits the action of acetylcholine on muscarinic receptors in peripheral tissues. This leads to a reduction in smooth muscle spasms, secretion, and motility, which makes the drug useful in treating conditions such as peptic ulcers, irritable bowel syndrome, and bladder spasms.

Due to its quaternary ammonium structure, homatropine methylbromide does not readily cross lipid membranes, including the blood-brain barrier. This pharmacokinetic feature distinguishes it from tertiary amine analogs like atropine or scopolamine, which can cause central nervous system effects such as sedation or hallucinations. As a result, homatropine methylbromide has a more limited side-effect profile with respect to the CNS, making it preferable in certain clinical situations where peripheral anticholinergic activity is needed without central effects.

In some formulations, homatropine methylbromide has been combined with mild analgesics (such as paracetamol or codeine) to enhance relief from gastrointestinal discomfort. However, due to regulatory changes and evolving standards of care, these combination products are less frequently used today.

The compound is administered orally in tablet or liquid form. Common dosages range from 1 to 2 milligrams taken several times a day, depending on the indication and patient response. Because of its anticholinergic action, typical side effects may include dry mouth, decreased sweating, urinary retention, blurred vision, and constipation. Contraindications include glaucoma, prostatic hypertrophy, and certain cardiac conditions where parasympathetic blockade is undesirable.

In analytical chemistry, homatropine methylbromide can be characterized using spectroscopic techniques such as nuclear magnetic resonance (NMR), infrared (IR) spectroscopy, and mass spectrometry. It exhibits typical absorption bands in IR for ester and amine functionalities, and NMR can confirm the presence of its tropane ring and methylated nitrogen.

Regulatory agencies in several countries list homatropine methylbromide as an approved drug substance for specific medical uses, though it is not as commonly prescribed today as other antispasmodic or anticholinergic medications. Its use has declined in favor of newer agents with more selective profiles or improved tolerability.

In summary, homatropine methylbromide is a quaternary ammonium muscarinic antagonist developed as a safer alternative to tertiary anticholinergics. Its inability to cross the blood-brain barrier and its strong peripheral anticholinergic effects have made it suitable for treating gastrointestinal and urinary tract disorders involving smooth muscle spasms. Though its clinical use has become less common, it remains a well-established compound in the history of antimuscarinic pharmacology.

References

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2011. An old drug for use in the prevention of sudden infant unexpected death due to vagal hypertonia. European Journal of Pediatrics, 170(12).
DOI: 10.1007/s00431-011-1544-0

2016. Preparation of a β-Cyclodextrin-Based Open-Tubular Capillary Electrochromatography Column and Application for Enantioseparations of Ten Basic Drugs. PLOS ONE, 11(1).
DOI: 10.1371/journal.pone.0146292