|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||Controlled (S8) (AU) Schedule I (US) BtM Anlage III (Germany)|
|Half-life||4 - 6 hours|
|(what is this?)|
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.
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 metabolite nortilidine and then to bisnortilidine. It is the (1S,2R)-isomer that is responsible for its analgesic activity
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.
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 are separated subsequently from the mixture by precipitation of the inactive (Z)-(cis)-isomers as zinc complex. The inactive (Z)-(cis)-isomers may be epimerized to the more thermodynamically favoured (E)-(trans)-isomers via reflux in diluted phosphoric acid.
- Martindale: The Complete Drug Reference
- Waldvogel, H. H. (2001). Analgetika, Antinozizeptiva, Adjuvanzien: Handbuch für die Schmerzpraxis (in German). ISBN 978-3-540-65796-5.
- Buschmann, H. (2002). Analgesics: From Chemistry and Pharmacology to Clinical Application. Wiley-VCH. ISBN 978-3-527-30403-5.
- Schulz, R.; Bläsig, J.; Wüster, M.; Herz, A. (1978). "The Opiate-Like Action of Tilidine is Mediated by Metabolites". Naunyn-Schmiedeberg's Archives of Pharmacology 304 (2): 89–93. PMID 212687.
- Drug Discovery and Commercial Exploitation Gerhard Satzinger Drug News Project psges 200-201 14(4) May 2001
- Fachinfo (SPC) for Valoron N (in German)
- Tings, T.; Trenkwalder, C. (2003). "When L-Dopa Preparations, Dopamine Agonists or Opioids? Therapy of Restless Legs Syndrome". MMW Fortschritte der Medizin (in German) 145 (10): 48–49. PMID 12688028.
- US patent 3557127, Satzinger, G., "Substituted Cyclohexenes, Derivatives thereof and Processes for Obtaining Same", issued 1971-01-19