morphinans and Acidosis

The objective of this study is to investigate the therapeutic effect of sinomenine (SIN) on rat cerebral ischemia-reperfusion (IR) injury and the molecular mechanism.. One hundred thirty-five rats were equally randomized into sham-operated group, middle cerebral artery occlusion (MCAO) group, and SIN group, and reversible rat MCAO model was made according to the Longa method for the MCAO and SIN groups. Then, 15 rats from each group were decapitated at 6, 12, and 24 hours after reperfusion to obtain brain tissue samples. Rats in the SIN group were injected with sinomenine by tail vein (90 mg/kg) 1 hour before ischemia; rats in the MCAO and sham-operated groups were administrated with the same volume of saline. Neurological severity score (NSS), infarction volume, ischemic brain water content, and blood-brain barrier (BBB) permeability were determined at corresponding time points. Acid-sensing ion channel (ASIC) 1a mRNA level was determined by quantitative real-time polymerase chain reaction; ischemic brain contents of lactic acid (LD), lactic dehydrogenase (LDH), ATPase, and inflammatory factors were determined by spectrophotometric method.. At 12 hours after reperfusion and since then, NSS in the SIN group decreased obviously; infarction volume, brain water content, and BBB permeability in the SIN group were lower than those in the MCAO group (P < .05). IR injury resulted in the upregulation of the contents of ASIC1a mRNA, LD, LDH, and inflammatory factors and the downregulation of the contents of ATPase, while SIN could reverse the upregulation/downregulation effect induced by IR injury (P < .05).. Through its anti-inflammation effect, which alleviates acidosis, improves energy metabolism, and inhibits ASIC1a level, SIN protects ischemic rat brain against cerebral IR injury.

Topics: Acid Sensing Ion Channels; Acidosis; Animals; Anti-Inflammatory Agents; Blood-Brain Barrier; Brain; Capillary Permeability; Cytoprotection; Disease Models, Animal; Energy Metabolism; Infarction, Middle Cerebral Artery; Inflammation Mediators; Male; Morphinans; Neuroprotective Agents; Rats, Sprague-Dawley; Reperfusion; Reperfusion Injury; Time Factors

The cardiac electrophysiological effects of 16-methylcyprenorphine (M8008), nor-binaltorphimine (NBT) and naltrexone, which are relatively specific opioid antagonists for delta, kappa and mu receptors, respectively, were studied in paced (1.5 Hz) sheep Purkinje fibres in vitro. M8008 (1 ng ml-1-10 micrograms ml-1) caused a concentration-dependent reduction in the maximum rate of depolarisation of phase 0 (MRD) and in the action potential duration measured at 50% repolarisation, APD50. Neither NBT (10 ng ml-1-10 micrograms ml-1) nor naltrexone (1 ng ml-1-10 micrograms ml-1) produced any significant effect on the cardiac action potential. In the presence of a physiological salt solution modified to mimic some of the changes that occur during myocardial ischaemia (i.e. hypoxia, acidosis, hyperkalaemia), M8008 caused a more marked reduction in MRD and prolonged rather than shortened APD50. These results suggest that the reported antiarrhythmic activity of M8008, but not NBT or naltrexone, may be, at least in part, explained by a direct cardiac electrophysiological action.

Topics: Acidosis; Action Potentials; Animals; Coronary Disease; Hyperkalemia; Hypoxia; Morphinans; Naltrexone; Narcotic Antagonists; Purkinje Fibers; Sheep

The efficacy of the neuroleptanalgesic combinations of fentanyl-fluanisone with diazepam; and etorphine-methotrimeprazine, either alone, or with diazepam, was investigated in the rabbit. The effects of these drugs on some cardiovascular variables were studied in chronically catheterized rabbits. Fentanyl-fluanisone and diazepam produced good surgical anaesthesia. Although respiratory depression occurred, this had little effect on blood gas values. In contrast, etorphine-methotrimeprazine and diazepam produced severe respiratory depression with consequent hypercapnia and acidosis.

Topics: Acidosis; Animals; Butyrophenones; Diazepam; Drug Combinations; Etorphine; Fentanyl; Hypercapnia; Methotrimeprazine; Morphinans; Neuroleptanalgesia; Rabbits; Respiration; Time Factors

Topics: Acidosis; Blood Proteins; Buprenorphine; Female; Humans; Middle Aged; Morphinans; Postoperative Complications; Protein Binding; Respiratory Insufficiency; Time Factors