The following information is based on studies of tramadol alone or acetaminophen alone, except where other-wise noted:
Tramadol is a centrally acting synthetic opioid analgesic. Although its mode of action is not completely under-stood, from animal tests, at least two complementary mechanisms appear applicable: binding of parent and M1 metabolite to µ-opioid receptors and weak inhibi-tion of reuptake of norepinephrine and serotonin. Opioid activity is due to both low affinity binding of the parent compound and higher affinity binding of the O-demethylated metabolite M1 to µ-opioid receptors. In animal models, M1 is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in µ-opioid binding.
Tramadol-induced analge-sia is only partially antagonized by the opiate antago-nist naloxone in several animal tests. The relative contribution of both tramadol and M1 to human anal-gesia is dependent upon the plasma concentrations of each compound (see CLINICAL PHARMACOLOGY, Pharmacokinetics).
Tramadol has been shown to inhibit reuptake of nor-epinephrine and serotonin in vitro, as have some other opioid analgesics. These mechanisms may contribute independently to the overall analgesic profile of tramadol.
Apart from analgesia, tramadol administration may pro-duce a constellation of symptoms (including dizziness, somnolence, nausea, constipation, sweating and pru-ritus) similar to that of other opioids.
Acetaminophen is a non-opiate, non-salicylate analgesic.
Tramadol is administered as a racemate and both the [-] and [+] forms of both tramadol and M1 are detected in the circulation. The pharmacokinetics of plasma tram-adol and acetaminophen following oral administration of one ULTRACET tablet are shown in Table 1. Tramadol has a slower absorption and longer half-life when com-pared to acetaminophen.