Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The functions of the central monoamines Norepinephrine (NE) and Serotonin (5HT) can be clarified by the study of behaviors of rats administered selective monoamine toxins. In his home environment the low NE rat has drive deficits and is lethargic, tending to remain in his burrow, but in novel environments this animal acts less frightened than Controls. The low 5HT rat is conversely active and exploratory in familiar environments but frightened in novel environments. These two animals model aspects of depression and anxiety, respectively. 5HT can be thought of as placing the brain into a state of consciousness appropriate for an animal in his nest (i.e., 5HT neurons act as relaxers), and as involved in a type of positive affect related to security, whereas NE neurons are dominant when an animal is vigilant, foraging out in the environment and are involved in a type of positive affect related to goal-directed approach arousal. Monoamine toxins may be produced when the behaviors elicited by these central neuronal systems are negatively reinforced (extinguished).
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PMID:Behavior and the balance between norepinephrine and serotonin. 123 10

The purpose of the present study was to develop a controllable experimental model in the dog that would consistently and predictably produce a malignant hypertensive crisis, and to determine the sequential changes in renal function, salt and water balance, and hormones that are involved in the transition from benign to accelerated hypertension. Norepinephrine (NE) was infused continuously into the renal artery of unilaterally nephrectomized dogs that were maintained on 50 mEq sodium/day. The infusion rate of NE was increased each day according to the following schedule: 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 microgram/kg/min. During the first 4 to 5 days of intrarenal NE infusion, there was a progressive decrease in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), and increases in plasma renin activity (PRA), mean arterial pressure (MAP), and filtration fraction. At the end of this period of benign hypertension, MAP had risen from a control value of 91 +/- 4 to 132 +/- 8 mm Hg, in association with approximately a 10-fold increase in PRA and a 40% reduction in renal function. Then, suddenly, during the subsequent 24-hour infusion period, the MAP increased abruptly in all animals (MAP = 156 +/- 8 mm Hg), and a hypertensive crisis occurred. This crisis was associated with the following: salt and water depletion, hyponatremia, hypovolemia and hemoconcentration, polydipsia, marked activation of the renin-angiotensin-aldosterone system, increased plasma cortisol concentration, hemolysis, marked impairment in renal function, lethargy, and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Malignant hypertensive crisis induced by chronic intrarenal norepinephrine infusion. 637 96

A variety of agents are currently used to treat the different anxiety disorders. Benzodiazepines, such as diazepam, are still preferred by some for the treatment of acute anxiety, with the advantage of a rapid onset of action, but they are less suitable for long-term treatment due to their potential for memory disturbances, sleepiness, lethargy, physical dependence and withdrawal. Compounds acting on monoamine neurotransmission are more suitable in the treatment of long-term or chronic anxiety disorders. Tricyclic antidepressants, such as imipramine, and monoamine oxidase inhibitors have been shown to be effective anxiolytics, but their side effects and safety concerns have limited their use. The probable role of disturbed serotonergic neurotransmission in anxiety is widely accepted and is the theoretical basis for the use of serotonergic agents such as the 5-HT1A receptor partial agonist, buspirone, and the selective serotonin reuptake inhibitors (SSRI), such as sertraline and paroxetine, which have largely replaced the earlier antidepressants. There is clear evidence for decreased serotonergic function in anxiety as well as in depression. Studies of patients with anxiety disorders show reduced levels of serotonin in cerebrospinal fluid (CSF) as well as reduced serotonin transporter binding. The role of noradrenaline in the control of anxiety is less well understood, although there is considerable evidence to suggest that a disturbance of noradrenergic neurotransmission may also contribute to the symptoms of anxiety. Noradrenaline modulates the activity of brain regions such as the amygdala which are associated with anxiety. In addition, anxiety states are associated with increases in the metabolite of noradrenaline, 3-methoxy-4-hydrophenylglycol (MHPG), and hypersecretion of noradrenaline in plasma and CSF. It appears likely that modulation of both serotonin and noradrenaline systems by dual-reuptake inhibitors may prove to be an advantage in the treatment of anxiety disorders. The serotonin-noradrenaline reuptake inhibitors (SNRI), venlafaxine, milnacipran and duloxetine are efficacious in relieving anxiety symptoms within depression, and some have proven efficacy in certain anxiety disorders. Initial studies suggest that dual acting agents may have an advantage over selective reuptake inhibitors in certain anxiety disorders, such as post-traumatic stress disorder (PTSD), and in patients with comorbid anxiety and depression.
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PMID:Serotonin noradrenaline reuptake inhibitors: A new generation of treatment for anxiety disorders. 2492 77