Dopamine is necessary to endogenous morphine formation in mammalian brain in vivo.

Morphine, the most used compound among narcotic analgesics, has been shown to be endogenously present in different mammalian/invertebrate normal tissues. In this study, we used mice that cannot make dopamine due to a genetic deletion of tyrosine hydroxylase specifically in dopaminergic neurons, to test the hypothesis that endogenous dopamine is necessary to endogenous morphine formation in vivo in mammalian brain. When dopamine was lacking in brain neurons, endogenous morphine was missing in brain mouse whereas it could be detected in brain from wild type rodent at a picogram range. Our data prove for the first time that endogenous dopamine is necessary to endogenous morphine formation in normal mammalian brain. Morphine synthesis appears to be originated from dopamine through L-tyrosine in normal brain tissue. Morphine synthesis is not considered to occur inside the same neuron in normal tissue; released dopamine might be transported into morphinergic neuron and further transformed into morphine. A physiological role for endogenous morphine is suggested considering that dopamine could modulate thermal threshold through endogenous morphine formation in vivo. Thus, dopamine and endogenous opiates/opioid peptides may be interconnected in the physiological processes; yet, endogenous morphine may represent a basic link of this chain.

Effect of combined exposure to carbon monoxide and cyanides in selected forensic cases.

Carbon monoxide is a toxic gas with potentially lethal action, which forms as a result of incomplete combustion in conditions where there is a lack of oxygen and which, therefore, is present in varying percentages in environments where fire develops. In addition to carbon monoxide, other factors such as cyanide may contribute or might actually be the primary cause of a subject's demise. In cases of exposure to both substances, the role of cyanide as a toxic/lethal agent in death by asphyxiation is still not clear: some authors attribute a primary action to such a gas in causing the demise, others consider carbon monoxide to be the only cause of the lethal event. For this reason it is in the interest of forensic medicine to study all lethal cases of exposure to toxic substances originating from fires of various types of materials, in order to determine information regarding kinetic action and the possible strengthening of the effect of the two substances. Two case studies are presented here, in which the results of the toxicological examinations are quite different, and the contributions of CO and HCN in a fire asphyxiation are considered.

Effects of endogenous morphine deprivation on memory retention of passive avoidance learning in mice.

Memory and the processes of learning in mammals are well known to be affected by opioid agonists such as morphine, which has been proven to interfere and cause amnesia. The presence of endogenous morphine has been demonstrated in various tissues from mammals to invertebrates. In this study, we have investigated the effects caused by in-vivo immunodepletion of endogenous morphine on working memory under different experimental conditions. When mice were submitted to fasting, a stress condition, acquisition and consolidation of memory were significantly impaired compared to controls. This was demonstrated by a decrease in entry latency into the dark room in the retention session of the passive avoidance test. This effect was significantly reversed to baseline values when endogenous morphine was depleted from the extracellular brain space. These findings support a role for endogenous morphine in weakening memory processes under stress conditions.

Suicide by buflomedil HCl: a case report.

A man was found dead in his bed by his relatives; a half-empty wrapping of Loftyl Plus (the trade name of a vasodilator medications containing buflomedil HCl marketed in Italy) was on the bedside table. GC/MS analysis of a blood sample collected during the autopsy revealed a buflomedil HCl concentration approximately of about 20 times the therapeutic values.

Endogenous morphine and codeine in the brain of non human primate.

BACKGROUND: Morphine is the most used compound among narcotic analgesics. Apart from its presence in the poppy plant, morphine has been shown to be endogenously present in different tissues of mammals and lower animals. MATERIAL/METHODS: The presence of endogenous morphine and codeine was investigated by Gas Chromatography/ Mass Spectrometry (GC/MS) in the brain of non human primate. The release of endogenous morphine from monkey brain slices was studied in vitro in the presence of high potassium concentrations with and without calcium in the medium. RESULTS: Endogenous morphine, and its direct precursor codeine, was for the first time detected by GC/MS in the brain of non human primate. High potassium concentrations depolarized neurons releasing endogenous morphine twofold above basal line levels in a calcium dependent mechanism. CONCLUSIONS: This finding confirms the presence of the endogenous alkaloid throughout the phylogenesis of the nerve system of mammals and lower animals and indicates that endogenous morphine might function as a neuromodulator/neurotransmitter agent in the central nervous system (CNS) of non human primates.