Oxybuprocaine

Oxybuprocaine (INN), also known as benoxinate or BNX, is an ester-type local anesthetic, which is used especially in ophthalmology and otolaryngology. Oxybuprocaine is sold by Novartis under the brand names Novesine or Novesin.

Oxybuprocaine

Clinical data
Trade names	Novesin(e)
AHFS/Drugs.com	International Drug Names
Pregnancy category	AU: D
Routes of administration	Topical
ATC code	D04AB03 (WHO) S01HA02 (WHO)
Legal status
Legal status	BR: Class C1 (Other controlled substances)[1]
Pharmacokinetic data
Metabolism	Esterases in blood plasma and liver
Identifiers
IUPAC name 2-diethylaminoethyl 4-amino-3-butoxy-benzoate
CAS Number	99-43-4 Y
PubChem CID	4633
IUPHAR/BPS	7123
DrugBank	DB00892 Y
ChemSpider	4472 Y
UNII	AXQ0JYM303
KEGG	D08319 Y
ChEBI	CHEBI:309594 Y
ChEMBL	ChEMBL1200 Y
CompTox Dashboard (EPA)	DTXSID7048530
Chemical and physical data
Formula	C17H28N2O3
Molar mass	308.422 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C(OCCN(CC)CC)c1cc(OCCCC)c(cc1)N
InChI InChI=1S/C17H28N2O3/c1-4-7-11-21-16-13-14(8-9-15(16)18)17(20)22-12-10-19(5-2)6-3/h8-9,13H,4-7,10-12,18H2,1-3H3 Y Key:CMHHMUWAYWTMGS-UHFFFAOYSA-N Y
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Safety for use in pregnancy and lactation has not been established.

Uses

• In ophthalmology in order to numb the surface of the eye (the outermost layers of the cornea and conjunctiva) for the following purposes:^[2]
  • in order to perform a contact/applanation tonometry,
  • for small operations,
  • in order to remove small foreign objects from the uppermost layer of the cornea or conjunctiva;
• in otolaryngology for numbing the mucous membranes of the nostrils and pharynx, for diagnostic purposes and small operations,^[3]
• for numbing the mucous membranes of bronchi, for example in bronchoscopy,^[3]

Pharmacokinetics

Anaesthesia starts with a latency of 30 to 50 seconds and lasts for about 10 to 30 minutes, depending on perfusion. The drug is metabolised by esterases in blood plasma and liver.^[3]

Adverse effects

When used excessively, oxybuprocaine like any other topical anesthetic used in the eye and on mucous membranes (like for example tetracaine, proxymetacaine and proparacaine) can cause irritation, hypersensitivity, anaphylaxis, irreversible corneal damage and even complete destruction of the cornea.^[2][4] (Excessive use means several times a day during several days or even weeks.)

Interactions

Oxybuprocaine is incompatible with silver and mercury salts, as well as alkaline substances. It also reduces the antimicrobial action of sulfonamides.^[3]

Synthesis

Thieme Synthesis:^[5] Patent:^[6] Sino:^[7] Precursor patent:^[8]

The nitration of 3-hydroxybenzoic acid [99-06-9] (0) gives 3-hydroxy-4-nitrobenzoic acid [619-14-7] (1). Fischer esterification with ethanol gives ethyl 3-hydroxy-4-nitrobenzoate [717-01-1] (2). The phenoxide ion was then prepared from potash (3). Alkylation with 1-bromobutane supplied ethyl 3-butoxy-4-nitrobenzoate, CID:13346201 (4). The product is crystallized from hydrochloric acid, and then halogenation with thionyl chloride gives 3-butoxy-4-nitrobenzoyl chloride [23442-21-9] (5). Esterification with diethylaminoethanol [100-37-8] (6) gives 2-(diethylamino)ethyl 3-butoxy-4-nitrobenzoate, CID:13346204 (7) Lastly, catalytic hydrogenation over Raney-Nickel completes the synthesis of Oxybuprocaine (8).

See also

• Topical anesthetic