Tilidine

Tilidine

File:TilidineEnantiomers.svg
Systematic (IUPAC) name
A 1 to 1 mixture of (1R,2S)- and (1S,2R)-Ethyl 2-(N,N-dimethylamino)- 1-phenylcyclohex- 3-enecarboxylate
Legal status
Legal status	Schedule I (US); BtM Anlage III (Germany)
Pharmacokinetic data
Bioavailability	Oral: >90%
Metabolism	Hepatic demethylation
Biological half-life	4 - 6 hours
Excretion	Renal, 90%
Identifiers
CAS Number	51931-66-9
ATC code	N02AX01 (WHO)
Chemical data
Formula	C17H23NO2
Molar mass	273.37[[]]

Tilidine (INN, USAN), or tilidate (BAN) (Valoron, Valtran, Tilidin) is a synthetic opioid analgesic, used mainly in Germany, Switzerland and Belgium for treatment of moderate to severe pain, both acute and chronic.

Pharmacology

Considered a low- to medium-potency opioid, tilidine has the oral potency of about 0.2, i.e., a dose of 100 mg p.o. is equianalgesic to approximately 20 mg morphine sulfate orally. It is administered orally (by mouth), rectally (by a suppository), or by injection (s.c., i.m. or slowly i.v.) with single doses of 50 to 100 mg, the maximal daily dose being up to 600 mg.

Tilidine itself is only a weak opioid, but is rapidly metabolised in the liver and gut to its active metabolites nortilidine and bisnortilidine, which are fairly potent, µ-selective agonists.

Indications

Tilidine is used in the form of hydrochloride or phosphate salt. In Germany, tilidine is available in a fixed combination with naloxone for oral administration (Valoron N and generics); the admixture of naloxone is claimed to lower the abuse liability of the opioid analgesic. In Switzerland the original Valoron brand with only tilidine and no naloxone is also available.

As well as its use as an analgesic, tilidine is also commonly used in Germany for treatment of restless legs syndrome.

Synthesis

It is manufactured by a Diels-Alder reaction of 1-N,N-dimethylaminobuta-1,3-diene with ethyl atropate, yielding a mixture of isomers, of which only the (E)-(trans)-isomers are active and is separated subsequently from the mixture by precipitation of the inactive (Z)-(cis)-isomers as zinc complex.

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References

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