Considered a low-to-medium-potency opioid,<unk>  has the oral potency of about 0.2, that is, 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 (SC, IM or slowly IV).<unk>  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 (dextilidine) that is responsible for its analgesic activity. Nortilidine binds to opiate receptors in the central and peripheral nervous systems and suppresses pain perception and transmission. To counteract the abuse potential,<unk>  is used in combination with the opioid receptor antagonist naloxone. Naloxone abolishes the central depressant and peripheral effects of<unk> . The mixing ratio with naloxone is chosen so that the analgesic effect of<unk>  is not impaired. Pharmacokinetics==<unk>  is rapidly absorbed after oral administration and is subject to a pronounced first-pass effect. The conversion of<unk>  into the more active metabolite nortilidine occurs with the participation of CYP3A4 and CYP2C19. The inhibition of these enzymes can thus alter the efficacy and tolerability profile of<unk> . The analgesic effect occurs after 10-15 minutes. After oral administration of 100 mg<unk>  plus 8 mg naloxone, the maximum effect is reached in about 25-50 minutes. The duration of action is given as 4-6 hours. The elimination half-life for nortilidine is 3-5 hours.<unk>  is metabolised to 90% and eliminated renally. The rest appears in the faeces. Depending on the extent of the impairment, the maximum concentration of nortilidine in plasma is lower in insufficient liver function than in healthy individuals and the half-life is prolonged. In case of severe hepatic insufficiency the therapy is questionable. In these cases, it is possible that the formation of active nortilidine may be so low that the analgesic effect is insufficient. In addition, in the combination preparations with naloxone, the inactivation of the same can only be insufficient. The consequent antagonisation of the nortilidine effect can lead to a further loss of activity.
Tilidine
Iontocaine
Lidocaine
Etidocaine
Procaine
Articaine
Ibogaine
Quinidine