Fomocaine

Structural formula
General
Non-proprietary name	Fomocaine
other names	N - [3- (4-phenoxymethylphenyl) propyl] morpholine ( IUPAC )
Molecular formula	C 20 H 25 NO 2
Brief description	colorless and odorless crystals
External identifiers / databases
EC number	626-114-6
ECHA InfoCard	100.154.545
PubChem	71693
ChemSpider	64745
Wikidata	Q1435626
Drug information
ATC code	C05 AD59
Drug class	Local anesthetic
Mechanism of action	unspecific membrane expansion on the sodium channel
properties
Molar mass	311.4 g mol −1
Melting point	54–56 ° C (base); 173-175 ° C (hydrochloride);
pK s value	Base: 7.1
solubility	Base: practically insoluble in water; Hydrochloride: slightly soluble in water, soluble in chloroform , sparingly soluble in ethanol ;
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 302-317-318-400
	P: 273-280-305 + 351 + 338
Toxicological data	175 mg kg −1 ( LD 50 , mouse , iv )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Fomocaine is a morpholine - derivative that, as local anesthetic from the same class of Fomocaine, to 2003 as a surface anesthetic was used.

history

In the 1950s, the German pharmacist Herbert Oelschläger looked for stable and highly effective local anesthetics with low toxicity and found a useful component in the base morpholine. In 1967 fomocaine was introduced into therapy under the trade name Erbocain ^® . In 1979 the hydrochloride was included in the German Medicines Codex , and in 1991 that of the base.

Fomocaine was used in ointments and gels in dermatology and in suppositories for the treatment of the haemorrhoidal symptom complex. However, there have been no more preparations on the market since 2003.

pharmacology

Fomocaine acts on voltage-dependent sodium channels in the cell membranes of the nerve cell, both by blocking and by being embedded in the membrane (unspecific membrane expansion). It is also possible to block calcium channels in which fomocaine has a similar affinity to e.g. B. has flecainide .

The systemic toxicity is low compared to other local anesthetics such as tetracaine and lidocaine . One reason for this is the high level of plasma protein binding .

Pharmacokinetics

Protein binding

95% of fomocaine is bound to plasma proteins, the majority of which is bound to serum albumin . The affinity for this is mediated via the two aromatic rings and the alkylene group.

Biotransformation

Fomocaine is almost completely metabolized, less than 5% is excreted unchanged. The most important metabolites are 4-OH-fomocaine, fomocaine- N -oxide and 4-OH-fomocaine- N -oxide, a total of 13 are known. The derivative 2-hydroxy-fomocaine still has a clearly local anesthetic effect in the cornea test.

Individual evidence

↑ ^a ^b ^c Dahse, Thomas: Synthesis, pharmacodynamics and biotransformation of the fomocaine derivative Oe 9000 , p. 23ff. Dissertation (PDF, 3.8 MB).
↑ ^a ^b ^c Knauthe, Sophie: In-vitro studies on the influence of the microsomal cytochrome P450 system in the rat liver and on possible pro- and / or antioxidant properties of new fomocaine derivatives and some fomocaine metabolites compared to fomocaine, procaine, lidocaine , dissertation, p. 16-17.
^ ^A ^b Hunnius Pharmaceutical Dictionary 9th Edition 2004, ISBN 3-11-017475-8 , pp. 603-604.
↑ Entry on fomocaine. In: Römpp Online . Georg Thieme Verlag, accessed on June 19, 2014.
↑ ^a ^b FOMOCAINE data sheet from Sigma-Aldrich , accessed on April 2, 2011 ( PDF ).

↑ Herbert Oelschläger: The Fomocaine from a chemical, pharmacokinetic and pharmacological point of view: Current status and outlook. In: Pharmacy in our time . Volume 29, No. 6, pp. 358-364, doi : 10.1002 / 1615-1003 (200012) 29: 6 <358 :: AID-PAUZ358> 3.0.CO; 2-3 .

[Dahse-1] Dahse, Thomas: Synthesis, pharmacodynamics and biotransformation of the fomocaine derivative Oe 9000 , p. 23ff. Dissertation (PDF, 3.8 MB).

[Knauthe-2] Knauthe, Sophie: In-vitro studies on the influence of the microsomal cytochrome P450 system in the rat liver and on possible pro- and / or antioxidant properties of new fomocaine derivatives and some fomocaine metabolites compared to fomocaine, procaine, lidocaine , dissertation, p. 16-17.

[Hunnius-3] A ^b Hunnius Pharmaceutical Dictionary 9th Edition 2004, ISBN 3-11-017475-8 , pp. 603-604.

[Römpp-4] Entry on fomocaine. In: Römpp Online . Georg Thieme Verlag, accessed on June 19, 2014.

[Sigma-5] FOMOCAINE data sheet from Sigma-Aldrich , accessed on April 2, 2011 ( PDF ).

[6] Herbert Oelschläger: The Fomocaine from a chemical, pharmacokinetic and pharmacological point of view: Current status and outlook. In: Pharmacy in our time . Volume 29, No. 6, pp. 358-364, doi : 10.1002 / 1615-1003 (200012) 29: 6 <358 :: AID-PAUZ358> 3.0.CO; 2-3 .