Disulfiram is the commonly prescribed drug for the treatment of alcohol dependence. It's major metabolite (diethyldithiocarbamate) is an inhibitor of dopamine-betahydroxylase, an enzyme that catalyzes the metabolism of dopamine to norepinephrine resulting in psychosis. We recommend that disulfiram should be used at the lowest effective dose, possibly 250 mg daily and caution should be taken while prescribing disulfiram for patients with personal and familial antecedents of psychosis.
Alcoholism ; Disulfiram* ; Dopamine ; Humans ; Metabolism ; Norepinephrine ; Psychotic Disorders*

The catecholamine content was examined in the myocardium of dogs subjected to hemorrhagic hypotension of 40mmHg for a duration of one to hive hours respectively. No marked changes were noticed within two hours after production of homorrhagic hypotension but a significant reduction was found at the end of three hours of hypotension. The reduction of myocardial catecholamines was progressively pronounced with the prolonging the hypotensive period over three hours. Dogs were bled rapidly to an arterial blood pressure of 40mmHg and maintained at this hypotensive level for four hours, followed by reinfusion of the withdrawn blood. Eight out of 11 dogs succumbed within l2 hours, showing a 73 per cent mortality. The myocardial catecholamines in the surviving dogs returned almost to the normal level within 12-15 hours after the blood reinfusion, while those in the dogs which succumbed showed the same low level which was produced during hemorrhagic hypotension. It was also shown that the reduced myocardial catecholamines resulting from the hypotension will not be restored immediately after the reinfusion of the withdrawn blood. When norepinephrine was infused at a rate of five to seven microgram/kg/min for an hour before the reinfusion of the withdrawn blood, five out of six dogs died within 12 hours, showing a 82 per cent mortality. This result appears to indicate that norepinephrine infusion during oligemic hypotension may hasten death or not decrease the mortality of the animals. On the other hand, when norepinephrine was infused at a rate of three microgramkg/min for an hour following reinfusion of the withdrawn blood five out of 15 dogs died, indicating a significant increase of survival rate from hemorrhagic shock. The myocardial catecholamines of surviving dogs and dogs which succumbed following the administration of norepinephrine after blood reinfusion were similar respectively to those of dogs which survived and of dogs which died after blood reinfusion without norepinephrine. When norepinephrine (3 microgramkg/min) was infused for hour following blood reinfusion in the dogs pretreated with either dibenzyline (3mg/kg) or dichloroisoproterenol (1mg/kg), the beneficial effect of norepinephrine on the survival rate from hemorrhagic shock appeared to be absent. The efficacy of norepinephrine on the survival from hemorrhagic shock was discussed on the basis of myocardial catecholamine depletion.
Animals ; Catecholamines/*metabolism ; Dogs ; Epiphyses/*embryology ; Myocardium/*metabolism ; Norepinephrine/*pharmacology ; Shock, Hemorrhagic/*drug therapy

Animals ; Blood Pressure ; Lymphatic Vessels ; physiopathology ; Male ; Norepinephrine ; metabolism ; Rats ; Rats, Wistar ; Shock, Hemorrhagic ; metabolism ; physiopathology

The influence of thyroxine upon n the cardiac uptake of catecholamines was investigated in rabbits. A single injection of thyroxine(1.0m/kg) into rabbits did not affect the concentration of myocardial catecholamines. However, this dose of thyroxine greatly increased the cardiac uptake of catecholamine following injection of 2.0mg of norepinephrine as compared to that of untreated normal animals and it remained elevated for several hours. Similarly thyroxine also enhanced the accumulation of myocardial catecholamines following administration of dopa(60-80mg/kg) and epinephrine(1.0-1.5mg/kg).
Animal ; Catecholamines/metabolism* ; Epinephrine/metabolism ; Heart/drug effects* ; Male ; Myocardium/metabolism* ; Norepinephrine/metabolism ; Rabbits ; Thyroxine/pharmacology* ; Tritium

AIMTo elucidate the mechanism of depression induced by chronic unpredictable mild stress (CUMS), the effects of CUMS on serotonin (5-HT), tryptophan, stress hormones and behaviour were investigated in rats.

METHODSDepression was induced by for 8 weeks CUMS and confirmed by behavioral tests, the brain and plasma levels of monoamine neurotransmitters were analyzed by HPLC-ECD techniques, the content of plasma corticosterone was evaluated by I125 cortisol radioactivity immunoassay and the serum tryptophan content was measured by HTTACHI L-8800 amino acid analyzer.

RESULTS(1) Rats exposed to a series of mild, unpredictable stressors for 8 weeks displayed the decreased body weight, reduced scores of open-field test and preference of sucrose solution (P < 0.05). (2) Plasma and brain 5-HT contents in rats after exposure to CUMS 8 weeks decreased significantly (P < 0.05). While serum tryptophan content increased at the same time (P < 0.05). (3) Plasma norepinephrine and epinephrine in rats were increased after CUMS 8 weeks, but there was no difference between control and CUMS group in plasma corticosterone.

CONCLUSIONThe behavioral changes induced by CUMS for 8 weeks are similar to the features of human depression, which may be related to the disturbances of tryptophan metabolism induced by increased norepinephrine and epinephrine in CUMS rat.

Animals ; Depression ; metabolism ; Epinephrine ; metabolism ; Hippocampus ; metabolism ; Male ; Neurosecretory Systems ; metabolism ; Norepinephrine ; metabolism ; Rats ; Rats, Wistar ; Serotonin ; metabolism ; Stress, Psychological ; metabolism

In view of the effective traditional Chinese medicine (TCM) in the treatment of clinical depression, the mechanism is not clear, this study attempts to research the cause of depression in a complex situation to lay the foundation for the next step of TCM curative effect evaluation. Based on the brain wave of 120 depression patients and 40 ordinary person, the change regulation of acetylcholine, dopamine, norepinephrine, depression neurotransmitters and excited neurotransmitters in the whole and various encephalic regions' multi-neurotransmitters of depression patients-serotonin are analysed by search of encephalo-telex (SET) system, which lays the foundation for the diagnosis of depression. The result showed that: contrased with the normal person group, the mean value of the six neurotransmitters in depression patients group are: (1) in the whole encephalic region of depression patients group the dopamine fall (P < 0.05), and in the double centralregions, right temporal region and right parietal region distinct fall (P < 0.01); (2) in the right temporal region of depression patients group the serotonin rise (P < 0.05); (3) in the right central region, left parietal region of depression patients group the acetylcholine fall (P < 0.05), left rear temporal region fall obviously (P < 0.01). The correlation research between antagonizing pairs of neurotransmitters and neurotransmitters: (1) the three antagonizing pairs of neurotransmitters-serotonin and dopamine, acetylcholine and norepinephrine, depression neurotransmitters and excited neurotransmitters, in ordinary person group and depression patients group are characterizeed by middle or strong negative correlation. Serotonin and dopamine, which are characterized by weak negative correlation in the right rear temporal region of ordinary person group, are characterized by strong negative correlation in the other encephalic regions and the whole encephalic (ordinary person group except the right rear temporal region: the range of [r] is [0.82, 0.92], P < 0.01)/(depression patients group:the range of [r] is [0.88, 0.94], P < 0.01); acetylcholine and norepinephrine, in the whole and various encephalic region are characterized by middle negative correlation(ordinary person group:the range of [r] is [0.39, 0.76], P < 0.01 or P < 0.05)/(depression patients group: the range of [Ir] is [0.56, 0.64], P < 0.01); depression neurotransmitters and excited neurotransmitters are characterized by middle strong negative correlation (ordinary person group: the range of [r] is [0.57, 0.80], P < 0.01)/(depression patients group: the range of [r] is [0.68, 0.78], P < 0.01). (2) The two neurotransmitters which are not antagonizing pairs of neurotransmitters, serotonin and excited neurotransmitters, or acetylcholine and depression neurotra-nsmitters, or dopamine and depression neurotransmitters in the various encephalic regions are characterized by weak negative correlation. Serotonin and excited neurotransmitters are characterizeed by weak negative correlation (ordinary person group: in the right central region, left parietal region, double front temporal regions, right rear temporal region, the range of [r] is [0.25, 0.50], P < 0.01 or P < 0.05)/(depression patients group: in the whole encephalic regions, double parietal regions, double occipital regions, right front temporal region, left central region, left frontal region, the range of [r] is [0.18, 0.37], P < 0.01 or P < 0.05); acetylcholine and depression, neurotransmitters are characterized by weak negative correlation (ordinary person group: in the double frontal regions, left parietal region, left front temporal region, right rear temporal region, the range of [r] is [0.31, 0.46], P < 0.01 or P < 0.05)/(depression patients group: in double rear temporal regions, right front temporal region, double occipital regions, left central region, the range of [r] is [0.20, 0.32] , P < 0.01 or P < 0.05); do-pamine and depression neurotransmitters are characterized by weak middle negative correlation (ordinary person group: in left parietal region, right central region, left frontal region, left occipital region, double front temporal regions, the range of [r] is [0.33, 0.68], P < 0.01 or P < 0.05)/(depression patients group: in the whole region and other various regions except the left frontal region, right central region, the range of Irl is [0.21, 0.34], P < 0.01 or P < 0.05). Dopamine and acetylcholine or norepinephrine and serotonin are characterized by weak positive correlation in all encephalic regions. Dopamine and acetylcholine are characterized by weak positive correlation (ordinary person group: in left frontal region, right parietal region, left front temporal region and left rear temporal region, the range of [r] is [0.37, 0.46], P < 0.01)/(depression patients group: in the whole region and the orther various regions except the double central regions, the range of [r] is [0.23, 0.5], P < 0.01 or P < 0.05); norepinephrine and serotonin are characterized by weak positive correlation (ordinary person group: in double front temporal regions, double rear temporal regions, right frontal region and left parietal region, the range of [r] is [0.34, 0.48], P < 0.01 or P < 0.05)/(depression patients group: in the whole and various regions, the range of [r] is [0.18, 0.42], P < 0.01). The main differences between the depression patients group and ordinary person group are: (1) In the whole regin, left frontal region and right central region of depression patients group, the six neurotransmitters all fall normally (P < 0.05). (2) The percent of dopamine falling or including dopamine falling, or including dopamine falling and serotonin rising in depression patients group increases. The percent of dopamine falling or including dopamine falling in the whole region, right frontal region, right central region increases (P < 0.01), such as dopamine decreasing, serotonin increasing dopamine decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing, dopamine decreasing norepinephrine increasing depression neurotransmitters decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing and so on. (3) The percent of acetylcholine falling, or including acetylcholine falling, or including acetylcholine falling and neurotransmitters (beta)-receptor)rising in depression patients group increases. The percent of acetylcholine falling, or including acetylcholine falling in the right temporal region, double central regions increases (P < 0.05 or P < 0.01), such as acetylcholine decreasing, acetylcholine decreasing neurotransmitters increaseng, acetylcholine decreasing neurotransmitters increasing depression neurotransmitters decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing and so on. It's showed in research that depression patients' brain are characterized by multi-neurotransmitters abnormal, the synchronous change of multi-neurotransmitters has some certain regularities, which are not the simple linear relation. It's conformed that the three antagonizing pairs, neurotransmitters-serotonin and dopamine, acetylcholine and norepinephrine, depression eurotransmitters and excited neurotransmitters of ordinary person group and depression patients group, are both characterized by strong antagonizing relation, that the two neurotransmitters which are not antagonizing pairs of neurotransmitters are characterized by weak positive correlation or negative correlation, prompt maybe has the indirect causal relationship. And the change of six neurotransmitters in depression patients' various encephalic regions is rather complex. It's conformed preliminarily that the right frontal region and right central region are characterized by dopamine decreasing, acetylcholine decreasing, serotonin increasing dopamine decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing, dopamine decreasing norepinephrine increasing excited neurotransmitters decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing, acetylchoine decreasing neurotransmitters increasing, acetylcholine decreasing neurotransmitters increasing excited neurotransmitters decreasing and so on. Contrasted with the ordinary person group, the depression patients group have the notable difference.
Acetylcholine ; metabolism ; Adolescent ; Adult ; Aged ; Brain ; metabolism ; Case-Control Studies ; Depression ; metabolism ; Dopamine ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Neurotransmitter Agents ; metabolism ; Norepinephrine ; metabolism ; Serotonin ; metabolism ; Young Adult

Acetylcholine ; metabolism ; Animals ; Arcuate Nucleus of Hypothalamus ; metabolism ; Dopamine ; metabolism ; Epinephrine ; metabolism ; Female ; Neurotransmitter Agents ; metabolism ; Norepinephrine ; metabolism ; Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; Synaptic Transmission

The data obtained from present experiments demonstrated that among several inhalation anesthetics, ether was the most irritable, resulting in marked irregularity of respiratory movement, and halothane depressed respiratory rate more than the other. The pulse rate and blood pressure were decreased marked1y in ether and the halothane anesthesia. the rate of beat of the isolated atria was not greately altered after anesthesia with ether or trichlore-thylene, while it was reduced after chloroform or halothane inhalation. The response of isolated atria to exogeneous norepinephrine was most prominent in the atria isolated from halothane anesthetized rabbits. Myocardial catecholamine contents were reduced uniformly after anesthesia with each anesthetics and most significantly with the halothane inhalation. From the above results, it may be concluded that the increasing cardiac activity with general inhalation anesthetics is closely related to the quantitative changes of the endogenous myocardial catecholamine contents.
Anesthesia, Inhalation/adverse effects ; Anesthetics/*toxicity ; Animals ; Catecholamines/*metabolism ; Heart/*drug effects ; Myocardium/*metabolism ; Norepinephrine/*pharmacology ; Rabbits

Oesity is a major global health problem. However, current therapeutic strategies for obesity are limited. Obesity results from an imbalance between energy intake and energy expenditure, and the treatment of obesity is based on the correction of this metabolic imbalance. Anti-obesity drugs can shift this balance in a favorable way by reducing food intake, altering metabolism, and by increasing energy expenditure. There is a growing consensus that pharmacotherapy is appropriate for many individuals who are unable to lose weight through less intensive measures. However, side effects may ensue phamacotherapy for obesity. Only two drugs (sibutramine and orlistat) are currently approved for the long-term treatment of obesity. Sibutramine inhibits the reuptake of serotonin and norepinephrine. Orlistat works by blocking the pancreatic lipase. However, phamarcotherapy may not be the ultimate resolution for obesity management. Because the underlying pathophysiology in each individual varies in many aspects, it is recommended to provide individualized and tailored medication in addition to other antiobesity supportive treatments.
Anti-Obesity Agents ; Consensus ; Drug Therapy ; Eating ; Energy Intake ; Energy Metabolism ; Health Expenditures ; Lipase ; Metabolism ; Norepinephrine ; Obesity* ; Serotonin

A large number of β-adrenergic receptor (β-AR) agonists and antagonists are widely used in the treatment of cardiovascular diseases and other diseases. Nonetheless, it remains unclear whether these commonly used β-AR drugs can activate downstream β- arrestin-biased signaling pathways. The objective of this study was to investigate β-arrestin2 recruitment effects of β-AR agonists and antagonists that were commonly used in clinical practice. We used TANGO (transcriptional activation following arrestin translocation) assay to detect the β-arrestin2 recruitment by β-AR ligands in HEK293 cell line (HTLA cells) stably transfected with tetracycline transactivator protein (tTA) dependent luciferase reporter and β-arrestin2-TEV fusion gene. Upon activation of β-AR by a β-AR ligand, β-arrestin2 was recruited to the C terminus of the receptor, followed by cleavage of the G protein-coupled receptors (GPCRs) fusion protein at the TEV protease-cleavage site. The cleavage resulted in the release of tTA, which, after being transported to the nucleus, activated transcription of the luciferase reporter gene. The results showed that β-AR non-selective agonists epinephrine, noradrenaline and isoprenaline all promoted β-arrestin2 recruitment at β1-AR and β2-AR. β1-AR selective agonists dobutamine and denopamine both promoted β-arrestin2 recruitment at β1-AR. β2-AR selective agonists procaterol and salbutamol promoted β-arrestin2 recruitment at β2-AR. β-AR non-selective antagonists alprenolol and pindolol promoted β-arrestin2 recruitment at β1-AR. β1-AR selective antagonists celiprolol and bevantolol showed β-arrestin2 recruitment at β1-AR. β2-AR selective antagonists butoxamine showed β-arrestin2 recruitment at β1-AR. These results provide some clues for the potential action of β-AR drugs, and lay a foundation for the screening of β-arrestin-biased β-AR ligands.
Humans ; beta-Arrestin 2/metabolism* ; HEK293 Cells ; Adrenergic beta-Agonists/pharmacology* ; Isoproterenol/pharmacology* ; Receptors, Adrenergic, beta-2/metabolism* ; Norepinephrine/pharmacology*