Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extracellular and intracellular microelectrode studies were conducted to test the actions and interactions of naloxone and naltrexone, two supposedly "pure" opiate antagonists. Both were shown to depress excitability and action potential production when applied in relatively high concentrations. Low naltrexone concentrations antagonized the depression produced by naloxone, but low naloxone concentrations did not antagonize the depression produced by high naltrexone concentrations. Naltrexone also depressed the stimulus-induced increase in potassium conductance (gK) which naloxone did not do. Thus, the naloxone depression is mediated via an opiate drug receptor, whereas naltrexone in high concentrations produces a "local anesthetic-like" depression not involving the opiate drug receptor.
 ...
PMID:Naloxone and naltrexone: actions and interactions at an opiate drug receptor on frog skeletal muscle fibers. 22 Apr 7

The involvement of endogenous opioid mechanisms in the interaction between stress and ethanol was investigated in the rat. Animals were pretreated with naltrexone (10 mg/kg) or saline 3 h before a second injection consisting of ethanol (1.0 g/kg) or saline. They were then restrained for 15 or 60 min or left in home cages for an equivalent amount of time. After restraint, animals were either subjected to an open-field test or decapitated to collect blood for corticosterone determinations. Locomotor depression was found to be induced by 15 but not 60 min restraint. In naltrexone-treated animals, however, 60 min restraint was also found to induce locomotor depression. Ethanol pretreatment was found to block the locomotor depression induced by 15 min restraint. Such an interaction was in turn antagonized by naltrexone. In the 15 min condition, stress and ethanol were also found to interact in their effects on plasma levels of corticosterone. Naltrexone did not alter any effects of the stressors on corticosterone levels. These results provide support for the involvement of endogenous opioid mechanisms in the interaction of stress and ethanol at a behavioural level.
 ...
PMID:Involvement of endogenous opioid mechanisms in the interaction between stress and ethanol. 205 42

Morphine slows hepatobiliary elimination of sulfobromophthalein in rodents, raising dye levels in plasma and liver. Earlier studies showed these effects to be independent of other opiate effects such as bile duct spasm, hypothermia or blood gas changes resulting from respiratory depression. Because opiate receptors are distributed throughout the body, within the central nervous system and at peripheral sites including the gastrointestinal tract, experiments were performed to ascertain whether central or peripheral sites mediate the hepatobiliary effects of morphine. Sulfobromophthalein was administered intravenously to mice and its levels were measured in plasma and liver. Tail-flick latency indicated centrally mediated analgesia. Inhibited intestinal transit of India ink reflected an opiate effect with a significant peripheral component. When injected into a cerebral ventricle morphine was much more potent in producing analgesia and raising sulfobromophthalein levels than when administered intravenously or intraperitoneally. An intravenous dose of naloxone that reversed morphine analgesia also prevented sulfobromophthalein elevation but did not prevent gut slowing. Naltrexone injected in a cerebral ventricle also reversed analgesia and sulfobromophthalein elevation but not intestinal slowing. The polar opiate agonist N-methylmorphine did not cause analgesia or raise sulfobromophthalein levels at peripheral intraperitoneal doses to 100 mg/kg. When given in a central ventricle at 4 x 10(-3) mg/kg, this agent produced analgesia and raised sulfobromophthalein but did not slow intestinal transit. After spinal cord transection, intravenous morphine did not retard the tail-flick response or affect sulfobromophthalein disposition, but peripherally mediated intestinal transit was slowed as it was in intact mice. These experiments demonstrate parallel opiate effects on analgesia and on BSP disposition but not on intestinal transit.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Hepatobiliary effects of morphine are mediated in the brain. 217 93

An examination was made of the effect of REM sleep deprivation (REMSD) on some forms of altered motor activity, such as akinesia and catalepsy, induced by intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of morphine in adult, male Wistar rats. Administration of morphine (25 mg/kg i.p.) induced an akinetic-cataleptic syndrome and decreased spontaneous vertical motor activity (SVMA) in animals allowed undisturbed sleep. REMSD decreased the morphine-induced akinesia and catalepsy that are known to be mediated by an inhibitory mu-opiate system. The locomotor depressant action of morphine was converted to excitation (manifested as increased SVMA and hopping behavior) by REMSD. Similarly, decreased motor activity following i.c.v. administration of morphine (25 micrograms) was replaced by excitation in the form of jumping behavior after REMSD. Naltrexone (1 mg/kg i.p.) blocked the akinetic and cataleptic effects, but not the excitatory effects, of morphine. It is suggested that REMSD is associated with a functional insufficiency of an inhibitory mu-opiate system, thus unmasking the excitatory morphine effects. The proposed insufficiency of an endogenous opioid system might explain an increase in neuronal excitation during REMSD and the therapeutic effect of REM deficiency in some types of depression.
 ...
PMID:REM sleep deprivation antagonizes morphine-induced akinesia and catalepsy. 302 Jun 74

Hippocampal kindling results in tonic-clonic convulsions followed by a pronounced period of behavioural depression. The effect of the opiate antagonists, naltrexone and naloxone, on the duration of the after-discharge and behavioural depression was investigated. Naltrexone, injected s.c. 60 min before, significantly reduced the behavioural depression at doses as low as 0.6 mg/kg, but had no effect on the after-discharge even at higher doses. One day later, the behavioural depression was still reduced in some animals and the after-discharge was significantly decreased following the higher doses (0.24-0.48 mg/kg). Naloxone, injected s.c., 10 min before, significantly reduced the behavioural depression at a dose as low as 0.002 mg/kg and also reduced the duration of the after-discharge at some doses. Naloxone did not exert any significant effects 24 h later. Naltrexone, injected i.c. 60 min before kindling in a dose of 1 microgram, significantly attenuated the behavioural depression and had no effect on the after-discharge. The behavioural depression was still attenuated 24 and 48 h later. The involvement of mu-receptor-related endogenous opioid mechanisms in postictal brain processes is suggested. The long-term effects might be related to receptor 'activation' during the immediate period due to an interaction between the antagonist and the kindling experience.
 ...
PMID:Hippocampal kindling-induced after-discharge and behavioural depression: immediate and long-term attenuation by opiate antagonists. 340 32

Multiple lines of experimental evidence point to the involvement of endogenous opiates in appetite regulation. Post brain injury patients often exhibit driven eating behaviour. Since this problem fails to respond to behaviour modification, appetite suppressants, lithium, or any other usual approach, the use of the oral narcotic antagonist, Naltrexone, was given to three such patients. Naltrexone binds multiple opiate receptor sites in the hypothalamus, including the kappa receptors which have been implicated in appetite regulation, the use of this narcotic antagonist in hypothalamic hyperphagia appears to be a rational approach to this intractable problem. In this open trial, lasting from 4 1/2 to 9 months, the minimal effective dose appeared to be in the range of 100 mg per day. No side-effects (for example elevations in liver enzymes) were noted. All of the patients had an improved sense of well-being and their behaviours were less difficult to manage when on the Naltrexone. The significance of this preliminary trial is that narcotic antagonists may have a role in the treatment of brain-injured patients with bulimia. Also, Naltrexone may be useful in treating other maladaptive behavioural consequences of head trauma such as stealing, manipulation, demandingness, and depression. Likewise, the effects on the deranged endocrine system, such as the hypogonadism, are significant and deserve further exploration.
 ...
PMID:Naltrexone in organic bulimia: a preliminary report. 345 71

Naltrexone hydrochloride reportedly produces frequent dysphoria. This has led to speculation regarding the role of endorphins in the etiology of depression. Thirty-six subjects completed an 8-week trial of naltrexone or placebo with frequent mood assessments. No significant differences on POMS scales were noted for either subject group. One subject was discontinued from the study because of a severe dysphoric reaction. Naltrexone does not appear to significantly alter mood over a 2-month time course in nonaddicted, healthy individuals. Subpopulations of patients under physiological or psychological stress may react to naltrexone with dysphoric symptoms.
 ...
PMID:Naltrexone and dysphoria: a double-blind placebo controlled trial. 359 12

The interactions of naltrexone with the nicotinic acetylcholine receptor were studied electrophysiologically using the frog sciatic nerve-sartorius muscle and biochemically using membranes from the electric organ of Torpedo ocellata. At nanomolar concentrations naltrexone increased the peak amplitude of endplate currents with little change in the decay time constant. At micromolar concentrations there was a concentration-dependent depression of endplate current and miniature endplate current amplitudes and decay time constants. Decay time constant depression was enhanced with hyperpolarization. Only marginal curvature was induced in peak endplate current amplitude versus membrane voltage plots by naltrexone. Naltrexone had no effect on single channel conductance but decreased open channel lifetime, according to fluctuation analysis. Naltrexone alone (less than or equal to 3 microM) did not impair binding of [125I]alpha-bungarotoxin to the receptor in a fast pre-equilibration assay, but increased the ability of acetylcholine to displace [125I]alpha-bungarotoxin. The drug displaced the agonist-stimulated binding of [3H]perhydrohistrionicotoxin to the channel site. Biphasic functional changes in neuromuscular transmission can be attributed to an allosteric mechanism with increased agonist binding to the nicotinic receptor at nanomolar concentrations and caused a non-competitive blockade of the ionic channel at micromolar concentrations.
 ...
PMID:Interaction of narcotic antagonist naltrexone with nicotinic acetylcholine receptor. 365 49

Compared with naloxone, two opiate antagonists (naltrexone and S-20682) were tested in the intact dog in order to reverse respiratory depression, induced by fentanyl 50 micrograms kg-1 i.v. Respiratory rate and arterial blood-gases were measured at 5, 30, 60, 120, 180 and 240 min after the additional i.v. injection of the antagonist (1 microgram kg-1). Only S-20682, but not naloxone or naltrexone, prevented late (240 min) fentanyl-induced depression of respiratory drive. A late respiratory depression coincided with an increase in amplitudes and a reduction of frequency in electrical cortical activity (EEG). Naltrexone exhibited an antagonistic effect of duration twice (60 min) that of naloxone.
 ...
PMID:Prevention of late fentanyl-induced respiratory depression after the injection of opiate antagonists naltrexone and S-20682: comparison with naloxone. 612 81

The possible involvement of opiate receptors in the cardiovascular depression associated with hypovolemic shock was investigated. Opiate receptor blockade with naltrexone increased mean arterial pressure, cardiac output, stroke volume and left ventricular contractility in dogs bled to a mean arterial pressure of 45 mm Hg. Naltrexone also increased survival rate. At high doses, naltrexone adversely affected cardiac performance which may outweigh its advantages of greater potency and putatively longer action than naloxone, at least in the dog. Similar actions with another opiate antagonist gives further proof for endogenous opiate involvement in the cardiovascular pathophysiology of hypovolemic shock.
 ...
PMID:Naltrexone improves survival rate and cardiovascular function in canine hemorrhagic shock. 627 27


1 2 3 4 Next >>