Tilidine

drugbox

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IUPAC_name = A 1 to 1 mixture of (1"R",2"S")- and (1"S",2"R")-Ethyl 2-(N,N-dimethylamino)-1-phenylcyclohex-3-enecarboxylate
CAS_number = 51931-66-9
ATC_prefix=N02
ATC_suffix=AX01
C=17 |H=23 |N=1 |O=2
molecular_weight = 273.37
bioavailability = Oral: >90%
metabolism = Hepatic demethylation
elimination_half-life = 4 - 6 hours
excretion = Renal, 90%
legal_status = Schedule I (US); BtM Anlage III (Germany)

Tilidine (INN, USAN), or tilidate (BAN) (Valoron, Valtran, Tilidin) is a synthetic opioid analgesic, used for treatment of moderate to severe pain, both acute and chronic. [Martindale: The Complete Drug Reference] Considered a low- to medium-potency opioid, it 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. [Waldvogel: Analgetika, Antinozizeptiva, Adjuvanzien. (in german)] 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.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.] It is manufactured by a Diels-Alder reaction of 1-N,N-dimethylaminobuta-1,3-diene with ethyl atropate, yielding a mixture of isomers, [ [http://www.google.com/patents?id=ry8zAAAAEBAJ&dq=3649628 Robert M. Novack. Process for producing substituted cyclohexene compounds. US Patent 3649628] ] of which only the (E)-("trans")-isomer is active and is separated subsequently from the mixture by precipitation of the inactive (Z)-("cis")-isomer as zinc complex.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. [Fachinfo (SPC) for Valoron N (in german)]

Authorities in Germany have recently reported increased cases of Tilidine abuse. [ [http://www.welt.de/wissenschaft/medizin/article2165497/Modedroge_macht_super_aggressiv.html Tilidin: Modedroge macht super aggressiv - Nachrichten Wissenschaft - Medizin - WELT ONLINE ] ] It remains unclear if this is empirically true.

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