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 opioid peptide, [Met(5)]-enkephalin (termed opioid growth factor, OGF), is an autocrine growth factor that serves as a constitutively active inhibitory agent. OGF crosses the placenta and depresses DNA synthesis in the fetus. The role of OGF in pregnancy and parturition, and the influence exerted on prenatal and neonatal features of the offspring, were studied in rats. Females received daily injections of 10 mg/kg OGF throughout gestation; all offspring were cross-fostered to lactating noninjected dams at birth. No effects on the length of gestation, course of pregnancy, behavior of the pregnant dam, maternal weight gain, or food and water intake throughout gestation were recorded in OGF-treated mothers. Moreover, nociceptive response in these females was not altered by chronic OGF exposure, and no signs of physical dependence or withdrawal could be observed following a challenge by the opioid antagonist naloxone. Litter size and the number of live births per litter of OGF-treated mothers were reduced by 25% from control subjects and a fourfold increase in stillborns was noted for mothers receiving OGF compared to control levels. Histopathologic analysis confirmed the stillborns to have died in utero. OGF-exposed neonates were normal in body weight and crown-to-rump length, but these pups were observed to be lethargic and cyanotic, and had subnormal weights of many organs. Body weights of 10-, 15-, and 21-day-old OGF-exposed rats were reduced 11-27% from control levels. Wet and dry organ weights of the rats maternally subjected to OGF were decreased from control values in six of the eight organs evaluated at 10 days. At weaning, some organs were subnormal in weight. These data lead us to hypothesize that a native opioid peptide-OGF-is integral to certain aspects of maternal, neonatal, and postnatal well-being, and that disruptions in this opioid peptide have serious repercussions on the course of pregnancy and fetal outcome.
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PMID:Chronic exposure to the opioid growth factor, [Met5]-enkephalin, during pregnancy: maternal and preweaning effects. 1181 20

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