Pharmacology & toxicology
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Pharmacology & toxicology · Feb 2001
Differentiation of disulfiram effects on central catecholamines and hepatic ethanol metabolism.
Disulfiram is used in the treatment of chronic alcoholism, because of the unpleasant symptoms it provokes after ethanol intake. The underlying mechanism is believed to be the accumulation of acetaldehyde in the blood, due to inhibition of the liver aldehyde dehydrogenases. In addition, it is known that disulfiram also has some neurotoxic properties. ⋯ It is known that high doses of disulfiram may cause severe encephalopathy and peripheral neuropathy in humans, which could be attributed to the impairment of the metabolism of brain biogenic amines, due to inhibition of dopamine-beta-hydroxylase. Our experimental data show that disulfiram affects the level of brain biogenic amines at dose levels higher than those inhibiting the activity of aldehyde dehydrogenase. Therefore, in clinical practice 'disulfiram reaction' could still be achieved with a low dosage regimen not producing neurotoxicity
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Pharmacology & toxicology · Jan 1998
Comparative studies on the induction of muscle contracture in mouse diaphragm and Ca2+ release from sarcoplasmic reticulum vesicles by organotin compounds.
Effects of organotins, including triethyltin and tributyltin, on skeletal muscle were studied with diaphragm and isolated sarcoplasmic reticulum membrane vesicles. Triethyltin induced muscle contracture in mouse diaphragm while tributyltin had comparatively less potency and efficacy in inducing the muscle contracture. ⋯ Triethyltin dose-dependently induced Ca2+ release from sarcoplasmic reticulum vesicles and inhibited the Ca2+-ATPase activity. These results suggested that triethyltin induced contracture in mouse diaphragm was mainly by induction of Ca2+ release and inhibition of Ca2+ uptake of the internal Ca2+ storage site the sarcoplasmic reticulum, while the tributyltin induced contracture might be due to enhancement of extracellular Ca2+ influx which further induce the release of internal Ca2+ through the Ca2+-induced Ca2+ release mechanism.
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Pharmacology & toxicology · Dec 1997
Randomized Controlled Trial Clinical TrialPostoperative recovery after cholecystectomy by minilaparotomy: a randomized double-blind comparison between alpha-trinositol and placebo.
An opioid-sparing effect of alpha-trinositol (D-myo-inositol 1,2,6-trisphosphate) following cholecystectomy in otherwise healthy patients was suggested by a pilot study. In order to verify this result, pain, pain relief and nausea were studied in patients undergoing elective cholecystectomy by minilaparotomy. The patients were randomized using double-blind design to receive an intravenous infusion of either alpha-trinositol or sodium chloride (placebo) for eight hr after the operation. ⋯ Neither pressure pain thresholds, nor the walking distance differed between the patients given alpha-trinositol and placebo, respectively. There were significant reductions of peak expiratory flow and of pressure pain thresholds under both costal margins up to 72 hr after surgery compared to presurgery values. As a conclusion, no analgesic effect of alpha-trinositol at the dosage used was observed in the postoperative patients studied.
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Pharmacology & toxicology · Aug 1997
Comparative StudyToxicity of bupivacaine and ropivacaine in relation to free plasma concentrations in pregnant rats: a comparative study.
The relationship between free drug concentration and toxicity of bupivacaine and ropivacaine, a new local anaesthetic agent, was studied in a pregnant rat model. The compounds were given subcutaneously to rats in late pregnancy. Dose levels (bupivacaine 5.5 to 24 mg/kg and ropivacaine 5.3 to 26 mg/kg) were selected based upon the proposed human dosage and the known pharmacological activity of the compounds. ⋯ After 24 mg/kg of bupivacaine an increased postnatal loss of the offsprings were noticed, most likely due to impaired maternal care. Protein binding, at expected Cmax, were significantly lower for ropivacaine (around 49%) compared with bupivacaine (around 69%) at dose levels. The results suggest an increased safety margin before onset of toxic side effects after treatment with ropivacaine, compared to bupivacaine, in pregnant rase.
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Pharmacology & toxicology · Jul 1996
Disposition and analgesic effects of systemic morphine, morphine-6-glucuronide and normorphine in rat.
Morphine, morphine-6-glucuronide and normorphine were administered to male Sprague-Dawley-rats. Analgesic effect was estimated with the hot plate and spinal nociceptive reflex depression. After intraperitoneal administration the molar potency ratio of morphine-6-glucuronide/morphine was 1.7 estimated by the paw lick latency on the hot plate utilizing a linked pharmacokinetic-pharmacodynamic model. ⋯ Varea was 9.0 +/- 2.1, 0.8 +/- 0.2 and 4.9 +/- 1.4 L.kg-1 respectively. The slow absorption of morphine-6-glucuronide was illustrated by the mean Tmax-value of the 16 min. as compared with 9 min. for morphine and 10 min. for normorphine. It was possible to fit pharmacokinetic and pharmacodynamic data of behavioural analgesic effect of both morphine and morphine-6-glucuronide to a parametric model linking the sigmoid Emax model to standard pharmacokinetic equations.