Tilidine

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. 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. 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. 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)-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.