Tilidine
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|
|---|---|
| Systematic (IUPAC) name | |
| A 1 to 1 mixture of (1R,2S)- and (1S,2R)-Ethyl 2-(N,N-dimethylamino)- 1-phenylcyclohex- 3-enecarboxylate | |
| Clinical data | |
| AHFS/Drugs.com | International Drug Names |
| Pregnancy cat. | ? |
| Legal status | Schedule I (US); BtM Anlage III (Germany) |
| Pharmacokinetic data | |
| Bioavailability | Oral: >90% |
| Metabolism | Hepatic demethylation |
| Half-life | 4 - 6 hours |
| Excretion | Renal, 90% |
| Identifiers | |
| CAS number | 51931-66-9  |
| ATC code | N02AX01 |
| UNII | GY33N31E9Y  |
| ChEMBL | CHEMBL563449 |
| Chemical data | |
| Formula | C17H23NO2 |
| Mol. mass | 273.37 |
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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.[1]
Contents |
[edit] 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.[2]
Tilidine itself is only a weak opioid, but is rapidly metabolised in the liver and gut to its active metabolite nortilidine[3][4] and then to bisnortilidine.
[edit] 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.[5] 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.[6]
[edit] 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,[7] 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.[3]
[edit] References
- ^ Martindale: The Complete Drug Reference
- ^ Waldvogel: Analgetika, Antinozizeptiva, Adjuvanzien. (in german)
- ^ a b Buschmann: Analgesics.
- ^ Schulz R, Bläsig J, Wüster M, Herz A. The opiate-like action of tilidine is mediated by metabolites. Naunyn Schmiedebergs Archives of Pharmacology. 1978 Sep 12;304(2):89-93.
- ^ Fachinfo (SPC) for Valoron N (in german)
- ^ Tings T, Trenkwalder C. When L-Dopa preparations, dopamine agonists or opioids? Therapy of restless legs syndrome. (German) MMW Fortschritte der Medizin. 2003 Mar 6;145(10):48-9. PMID 12688028
- ^ Gerhard Satzinger. Substituted Cyclohexenes compounds, Derivatives thereof and Process for Obtaining Same US Patent 3557127
