Effects of tramadol and tilidine/naloxone on oral-caecal transit and pupillary light reflex

As has been demonstrated in binding studies the two opioids tilidine (CAS 2 7107-79-7)/naloxone (CAS 357-08-4) and tramadol (CAS 36282-47-0) differ in regard to their affinities to the opioid receptor site. Therefore it is of interest to evaluate whether such a difference in opioid affinity is also s een in the pharmacological effects of clinically relevant doses in man. Fol lowing institutional appl oval by the local ethical committee and informed consent: 12 volunteers received oral doses of tramadol (100 mg), tilidine/n aloxone (100 mg) and placebo, respectively, in a randomized, double-blind c ross-over design. In order to determine the degree of constipation, oral-ca ecal transit time was measured using the H-2-exhalation test. Additionally, in order to evaluate a centrally mediated effect, the response of the pupi l to light was quantified using the pupillary light reflex technique. Both, peripheral and central mediated effects were compared to placebo. Tramadol as well as tilidine/naloxone induced a significant (p < 0.05) prol ongation of oral-caecal transit when compared to placebo. However, prolonga tion of oral-caecal transit was significantly longer in the tilidine/naloxo ne (p < 0.05) than in the tramadol group. Compared to tramadol, the pronounced constipating effect of tilidine/naloxo ne is likely to be due to the 10 fold higher affinity of that drug to the p eripheral opioid receptor sites in the intestinal tract, which are responsi ble for normal propulsion. Such difference in binding is underlined by a ce ntral effect, the pupillary light reflex response. The amount of constricti on of the iris to light was reduced after both opioids. Again, tilidine/nal oxone significantly reduced (p < 0.001) the pupillary light reflex when com pared to tramadol. Other side effects such as tiredness, nausea, emesis and dry mouth were mor e often reported after tilidine/naloxone than after tramadol (40 %, versus 15 %; p < 0.05). Vertigo and perspiration were more often reported after tr amadol than after after tilidine/naloxone (58 % and 78 % versus 8 %: p < 0. 01). All these data support the findings that while tramadol is considered an opioid, it does not mediate its main clinical relevant properties via bi nding at the opioid receptor. More likely, due to its monoaminergic reuptak e mechanism, to a lesser extent opioidlike effects are induced.