Methods and findings in experimental and clinical pharmacology
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Methods Find Exp Clin Pharmacol · Jun 2003
Randomized Controlled Trial Clinical TrialTransdermal nicotine increases heart rate after endotracheal intubation.
Transdermal nicotine reduces perioperative withdrawal symptoms when smoking is forbidden. We evaluated the influence of a transdermal nicotine system on cardiovascular response after endotracheal intubation. The study design was prospective, randomized, double-blind and placebo- controlled. ⋯ Heart rate and noninvasive arterial pressures were recorded 1 min and 5 min after intubation. The transdermal nicotine system significantly increased heart rate compared with the control group without nicotine substitution. Since the transdermal nicotine system increases heart rate it should not be used if tachycardia is potentially dangerous, such as in patients with ischemic heart disease.
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Methods Find Exp Clin Pharmacol · May 2003
Fluoxetine suppresses morphine tolerance and dependence: modulation of NO-cGMP/DA/serotoninergic pathways.
Although the phenomenon of opioid tolerance and dependence has been widely investigated, neither opioid nor non-opioid mechanisms are completely understood. In view of the modulation of 5-HT transport into presynaptic terminals in the brain by nitric oxide (NO) via cGMP, and the existence of a tonic 5-HTergic inhibition of dopamine release, the present study investigated the effect of fluoxetine, a selective serotonin reuptake inhibitor, and NO modulators L-N(G)-nitroarginine methyl ester (L-NAME; NO synthase inhibitor) and L-Arginine (substrate for nitric oxide synthase) alone or in combination against morphine tolerance and dependence. Animals developed tolerance to the antinociceptive effect of morphine (10 mg/kg s.c. twice daily) on day 3 and the degree of tolerance was further enhanced on days 9 and 10. ⋯ Fluoxetine-induced suppression was potentiated by L-NAME and accentuated by L-Arginine. The results therefore suggest that a complex phenomenon such as morphine tolerance and dependence might involve close interplay of the NO-c GMP/5-HT/DA receptor system. To the best of the authors' knowledge, this is the first report to suggest targeting this cascade for amelioration of opioid tolerance and withdrawal syndrome.
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Methods Find Exp Clin Pharmacol · Jan 2003
Comparative StudyMechanism of antinociceptive effect of nimodipine in experimental diabetic neuropathic pain.
This study used streptozotocin-(STZ; 50 mg/kg, i.v.) diabetic rats and monitored the weekly thermal nociceptive thresholds for 8-week diabetes. Nimodipine (10 mg/kg i.p.) treatment initiated after 8 weeks of diabetes antagonized the hyperalgesic response in diabetic rats. However, insulin treatment showed a partial response in these animals. ⋯ These data suggest that diabetes-induced hyperalgesia may be the consequence of increased excitatory tone within the spinal cord. An increased release of glutamate and activation of the NMDA receptor would maintain the hyperalgesic state. Reduced activity of both opioidergic and GABAB ergic inhibitory systems might accelerate the increased excitation, thus contributing to the ongoing pain in diabetic rats.
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Methods Find Exp Clin Pharmacol · Apr 2002
Involvement of opioid delta (delta)- and kappa (kappa)-receptors in ischemic preconditioning in a rat model of myocardial infarction.
There is controversy in the literature regarding the involvement of opioid delta (DOP, OP1)- and kappa (KOP,OP2)-receptors in ischemic preconditioning (IPC). Previous studies on this subject in our laboratories and elsewhere have been performed on either isolated heart muscles of experimental animals, or in open-heart surgery rats. To highlight this problem, we introduced an in vivo model of myocardial infarction in rats, which not only allowed electrocardiographic and enzymatic evaluation, but also morphometric assessment of myocardial infarction. ⋯ It decreased the infarct size/area at risk by 44%, decreased occurrence of early arrhythmias by 77% and also decreased ventricular ectopic beats by 80%. The opioid delta- and kappa-receptor agonists used in this study significantly reduced (p < 0.05) early (2 h) postinfarction mortality by 22% and 19%, respectively. Further studies are in progress to differentiate between the role of opioid kappa 1- and kappa 2-receptors and the molecular mechanisms of the effects of both opioid delta- and kappa-receptors.
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Methods Find Exp Clin Pharmacol · Nov 2001
Safety and efficacy of low-dose amphotericin B lipid complex for empirical antifungal therapy of neutropenic fever in patients with hematologic malignancies.
Amphotericin B lipid complex (ABLC) has been investigated as an empirical antifungal treatment for neutropenic patients with persistent fever of unknown origin (FUO). We studied the safety and efficacy of low dose ABLC (1 mg/kg/day) for empirical treatment of neutropenic FUO. Sixty-one patients with hematologic malignancies developing 69 episodes of neutropenic FUO after chemotherapy or hematopoietic stem cell transplantation were included in the study. ⋯ Among 67 evaluable episodes, the response rate (resolution of fever during the period of neutropenia without developing a fungal infection) was 67%, while 33% were treatment failures. Low-dose ABLC is safe, well tolerated and seems to be at least as effective as c-AmB for empirical antifungal therapy of FUO. Randomized trials at this dose level comparing ABLC with c-AmB or other lipid formulations are warranted.