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Anesteziol Reanimatol. 1994 May-Jun;(3):12-3.
[Immunity state of oncological patients during long-term treatment with tramal]

[Article in Russian]

Novikov IuA, Kon'kov ShKh, Shumilov EI.

Narcotic analgesics have an inhibiting effect on the immunity and that is why their use for pain relief in cancer patients cannot be regarded as adequate. The effect of a new synthetic analgesic tramal (tramal hydrochloride) on the immune system has been studied. Cellular immunity indexes, immunoglobulin level, and phagocytic activity of neutrophils have been determined before treatment and 1 and 2 weeks after the treatment started. The data obtained have shown that tramal does not inhibit the immune system. It has been also noted that pain relief in cancer patients improved the indexes of cellular and humoral immunity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8080118&dopt=Abstract Tramadol online, Ultram

Arukoru Kenkyuto Yakubutsu Ison. 1994 Feb;29(1):40-51.
[Withdrawal characteristics following frequent intravenous administration of several opioids in rats]

[Article in Japanese]

Wakasa Y, Kawaguchi T, Yanagita T.

Central Institute for Experimental Animals, Preclinical Research Division, Kanagawa, Japan.

Characteristics of withdrawal signs of several opioids were compared in rats after short-term frequent intravenous infusions. Male Sprague-Dawley rats with catheters implanted in the jugular veins were infused with a fixed dose of a drug hourly for 72 hrs. Thirty min after the final infusion, naloxone 4 mg/kg, s.c. was administered and withdrawal signs were observed for 1 hr and the severity of the withdrawal signs was scored, classified into a behavioral sign score, autonomic sign score, and body weight loss score. As a result, total withdrawal scores of morphine, methadone, d-propoxyphene, loperamide, tramadol, and pentazocine were significantly higher than that of saline, with the highest score being observed for 4 mg/kg or more of morphine. The total score of ethylketocyclazocine was slightly but significantly higher than that of saline. Buprenorphine and thebaine produced no observable withdrawal signs. The behavioral sign score tended to be higher than the other 2 scores in the drugs showing relatively low but significant total scores such as tramadol, pentazocine, and ethylketocyclazocine, while the score of autonomic signs or the body weight loss tended to be higher in drugs showing high total scores. Thus, in the case of opioids, it is considered that the severity of withdrawal signs was mainly derived from the autonomic signs including diarrhea which may result in body weight loss.

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Br J Pharmacol. 1993 Sep;110(1):169-76.
Effects of the central analgesic tramadol and its main metabolite, O-desmethyltramadol, on rat locus coeruleus neurones.

Sevcik J, Nieber K, Driessen B, Illes P.

Department of Pharmacology, University of Freiburg, Germany.

1. Tramadol is a centrally acting analgesic with low opioid receptor affinity and, therefore, presumably additional mechanisms of analgesic action. Tramadol and its main metabolite O-desmethyltramadol were tested on rat central noradrenergic neurones of the nucleus locus coeruleus (LC), which are involved in the modulation of nociceptive afferent stimuli. 2. In pontine slices of the rat brain the spontaneous discharge of action potentials of LC cells was recorded extracellularly. (-)-Tramadol (0.1-100 microM), (+)-tramadol (0.1-100 microM), (-)-O-desmethyl-tramadol (0.1-100 microM) and (+)-O-desmethyltramadol (0.01-1 microM) inhibited the firing rate in a concentration-dependent manner. (+)-O-desmethyltramadol had the highest potency, while all other agonists were active at a similar range of concentrations. 3. (-)-Tramadol (10, 100 microM) was less inhibitory in brain slices of rats pretreated with reserpine (5 mg kg-1, 5 h before decapitation) than in controls. 4. The effect of (-)-tramadol (10 microM) was abolished in the presence of the alpha 2-adrenoceptor antagonist, rauwolscine (1 microM), whilst that of (+)-O-desmethyltramadol (0.3 microM) virtually disappeared in the presence of the opioid antagonist, naloxone (0.1 microM). (+)-Tramadol (30 microM) and (-)-O-desmethyl-tramadol (10 microM) became inactive only in the combined presence of naloxone (0.1 microM) and rauwolscine (1 microM). 5. In another series of experiments, the membrane potential of LC neurones was determined with intracellular microelectrodes. (-)-Tramadol (100 microM) inhibited the spontaneous firing and hyper-polarized the cells; this effect was abolished by rauwolscine (1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

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