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

Most antidepressant therapies require an initial period of sustained use before therapeutic effects are observed; the literature suggests that this may be due to alterations in either serotonergic or noradrenergic systems. To further explore the mechanism of action of antidepressants, the effect of 21-day drug treatment to rats on serotonin type 2 and beta-adrenergic receptors in fronto-parietal hemicortices was evaluated. Because the same brain was used to measure concomitant changes in both receptors, confounding effects due to inter-animal variability are reduced. The effect of a classical antidepressant drug, desmethylimipramine, was compared with two compounds which have more recently been used to treat depression, ie., adinazolam, a tirazolobenzodiazepine, and buspirone, a serotonin type 1A partial agonist, both of which possesses combined anxiolytic and antidepressant effects. The anxiolytic drug diazepam, a benzodiazepine devoid of antidepressant properties, was used as an active control treatment. Membrane binding studies showed that the maximal binding of [125I]cyanopindolol to beta-adrenoceptors was significantly decreased only by desmethylimipramine treatment. On the other hand, adinazolam and buspirone, as well as desmethylimipramine, decreased the maximal binding of [125I]7-amino-8-iodo-ketanserin binding to serotonin type 2 receptors. Diazepam was without effect on either receptor. These results suggest that down-regulation of serotonin type 2 receptors may be a common element in the mechanism of action of antidepressant therapies.
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PMID:Regulation of serotonin type 2 (5-HT2) and beta-adrenergic receptors in rat cerebral cortex following novel and classical antidepressant treatment. 166 41

Diazepam binding inhibitor (DBI) is a neuromodulatory peptide for gamma-aminobutyric acid (GABA) neurotransmission. Levels of DBI in cerebrospinal fluid (CSF) were found to be elevated in depressed patients, when compared to age- and sex-matched normal controls. Levels of the peptide, corticotropin-releasing hormone (CRH), in CSF have been found to be elevated in depressed patients. Significant positive correlations between levels of DBI and CRH in the CSF of depressed patients and normal controls were found. These data suggest the possibility that DBI may have a role in coordinating responses to stress in humans, in addition to its possible role in the pathophysiology of depression.
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PMID:Cerebrospinal fluid diazepam binding inhibitor in depressed patients and normal controls. 178 40

We compared ventilatory effects of the nonsedating anxiolytic buspirone with those of the sedating anxiolytic diazepam in nine normal men. Resting ventilatory parameters and ventilatory responses to CO2 rebreathing and inspiratory threshold loading were measured before and after placebo, diazepam, and buspirone. Placebo had no ventilatory effects. Diazepam had no effect on resting ventilation but depressed response to CO2. Buspirone had no effect on resting ventilation or CO2 response. During loading, buspirone did not alter the augmentation of mouth pressure; diazepam produced a trend toward less augmentation. Both anxiolytics altered the load compensation response for the group; in particular, an increase in ventilation during loading (seen in three of nine subjects) was suppressed by drug administration. Diazepam also markedly depressed one subject's loaded ventilation below unloaded ventilation. In summary, buspirone did not cause the depression of respiratory center chemosensitivity that was seen with diazepam and produced less depression of load compensation in normal subjects. This suggests that it may be a safer anxiolytic in patients with lung disease.
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PMID:Differing effects of the anxiolytic agents buspirone and diazepam on control of breathing. 190 82

In endoscopic monitoring and treatment of gastrointestinal disease, it is important that patients will accept repeated examination. They are less likely to do so if the procedure is remembered as distressing or uncomfortable, as is likely when it is performed under topical anaesthesia alone. The aim of conscious sedation is a lightly sedated patient, who is awake, cooperative on demand, amnesic, and free from anxiety and fear. Various drugs in low doses can be used to meet these criteria. Among these are phenothiazines, butyrophenones, barbiturate and non-barbiturate hypnotics, benzodiazepines, and the hypno-analgesic, ketamine. As benzodiazepines offer both sedative and profound amnesic and anxiolytic effects, these drugs are used for conscious sedation worldwide. Diazepam has been the 'gold standard' of sedation, but the more modern benzodiazepines, particularly midazolam, are now more commonly used. In general, benzodiazepines demonstrate a broad therapeutic range. In accordance with dose, however, sedative drugs may induce side-effects, such as drowsiness, lowering of blood pressure, and respiratory depression. In addition, some may induce more wide-ranging side-effects, such as histamine liberation and anaphylactic reactions, thrombophlebitis, and pain on injection. They may have severe drug interactions when used in combination with local anaesthetics, hypnotics and opioids. In older patients, lower doses are necessary for sedation. Sedative drugs should be administered slowly, to avoid haemodynamic and respiratory side-effects.
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PMID:Pharmacology of drugs for conscious sedation. 198 Nov 3

Diazepam (0.21 mg/kg; group 1) and midazolam (0.03 mg/kg; group 2) was applied for sedation in two groups of urological patients (n = 10 in each) requiring transurethral resection (urine bladder, prostata) using spinal or peridural anaesthesia. Before anaesthetic procedure, 500 ml hydroxyethyl starch were administered for precluding severe vascular depression. Patients receiving midazolam began to sleep within one minute. Heart rate dropped in both groups after injection of both benzodiazepines which was considered a physiological sleeping effect. No hypotensive reactions were registered. Using this therapy maximum PaO2 values of 14.9 kPa in group 1 (diazepam) were registered and of 14.0 kPa in group 2 (midazolam). During the operation all patients were arousable. Side-effects such as nausea, vomiting and confusion were not observed.
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PMID:[The effect of diazepam and midazolam on the circulation and respiration during spinal and peridural anesthesia]. 208 5

Experiments were performed in the adult normotensive rats of Wistar strain and in the genetically hypertensive rats of Koletsky type; measurements were carried out in both sexes. The behaviour of control and drug treated rats were traced in the holeboard and in the elevated plus-maze. In the control animals when compared to the normotensive rats of both sexes, the genetically hypertensive rats of both sexes show increased aversion towards open space and high in the elevated plus-maze (when the number of visits of centre and open arms is considered in the first session); the latter type of rats also show elevated total time of locomotor-exploratory activity in both sessions, reduced rate of intra-session habituation of locomotor-exploratory activity in both sessions, and decreased percentage of time spent head dipping in both sessions. Tranylcypromine treatment at the dose 5 mg/kg b. w. increased number of visits in centre and in open arms only in the second session in the normotensive males, and this drug shows decrease in the latter parameter in the second session in the genetically hypertensive females. Tranylcypromine increased time spent in centre and in open arms in the first session only in the genetically hypertensive males, in the second session this drug shows increase in time spent in centre and in open arms in the normotensive females and decrease in the genetically hypertensive females. Caffeine treatment at the dose 10 mg/kg b. w. remained without effect in both strains of rats and in both sessions in the elevated plus-maze, except the decrease in the number of entries in centre and in open arms in the first session in the normotensive females. Diazepam treatment at the dose 1 mg/kg b. w. shows "anxiolytic" effect i.e., increase number of visits and time spent in centre and in open arms in both sessions and in both sexes of the genetically hypertensive rats. Thus diazepam shown its "anxiolytic" effect in very profound and stable manner only in the animals which show CNS neurotransmitter abnormalities reminding the CNS neurochemical abnormalities in human forms of depression and anxiety. It is worthwhile to note that diazepam only in the latter mentioned strain of rats very profoundly elevates the percentage of time spent head dipping. Thus this drug elevates the reactivity towards stimuli which show biological sense for the rats, i. e., to look up the small and dark space. This type of reaction is decreased in the genetically hypertensive rats of both sexes relative to the control normotensive rats of Wistar strain.
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PMID:Validation of aversion towards open space and height as a measure of anxiety in the genetically based animal model of depression. 213 25

We report here a study of the effects of alprazolam on in vivo pituitary-adrenal function in jacketed nonrestrained nonhuman primates and on in vitro CRH release from rat hypothalami and ACTH release from rat dispersed anterior pituicytes. We undertook this study because alprazolam is the only benzodiazepine effective in treating both major depressive and anxiety disorders, and recent data suggest that the hypercortisolism of major depression reflects hypersecretion of CRH. Moreover, the intracerebroventricular administration of CRH can reproduce many of the components of the symptom complex of major depression, including not only hypercortisolism, but also hypothalamic hypogonadism, decreased libido, anorexia, and intense anxiety. As a comparison, we also assessed the effects of diazepam on in vitro CRH release, because in contrast to alprazolam, diazepam is effective in anxiety states but not in depression. Alprazolam (0.01-0.3 mg/kg, iv) produced a dose-dependent inhibition of both plasma ACTH and cortisol secretion in non-restrained adult male rhesus monkeys. Our in vitro studies showed that alprazolam significantly inhibited serotonin (5HT)-induced CRH release in a dose-dependent fashion (10(-10)-10(-5) M). Diazepam also inhibited 5HT-induced CRH release, but was 40 times less potent than alprazolam. Alprazolam was ineffective in blocking basal or CRH-induced ACTH release from rat dispersed anterior pituicytes, suggesting that its in vivo effects are through inhibition of CRH secretion. As expected, the inactive benzodiazepine ligand Ro 15-1788 inhibited the effects of alprazolam on 5HT-induced CRH release, but this occurred only at doses below 10(-7) M. Interestingly, when incubated alone in higher doses with our rat hypothalamic organ culture, Ro 15-1788, like alprazolam, produced a dose-dependent inhibition of 5HT-induced CRH release (10(-7)-10(-5) M), suggesting an agonistic action of Ro 15-1788 at the benzodiazepine receptor at higher concentrations. We conclude that alprazolam is capable of suppressing the primate pituitary-adrenal axis, and that this suppression most likely reflects suppression of the CRH neuron rather than of the pituitary corticotroph cell. We speculate that the enhanced capacity of alprazolam to suppress the CRH neuron relative to other benzodiazepines may contribute to its unique efficacy among this class of drugs in the treatment of major depression. The capacity of Ro 15-1788 to reverse alprazolam-induced suppression of the CRH neuron indicates that the effects of alprazolam are mediated at least in part via its interaction with the benzodiazepine component of the gamma-aminobutyric acidA macromolecular complex.
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PMID:In vitro and in vivo effects of the triazolobenzodiazepine alprazolam on hypothalamic-pituitary-adrenal function: pharmacological and clinical implications. 215 87

Nalbuphine hydrochloride, a semi-synthetic agonist antagonist opioid, has been used in an intravenous injection of 20 mg followed by Diazemuls not less than five minutes later as a premedication in 462 patients undergoing a range of radiological procedures over a 2 year period. In all but two patients excellent sedation was obtained and there were no episodes of respiratory depression nor cardiovascular disturbances.
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PMID:Nalbuphine hydrochloride (Nubain, DuPont) as premedication for radiological procedures. 203 69

The effects of conditioning stimulation of a mixed nerve in the leg, the common peroneal nerve (CPN), on the ipsilateral soleus H-reflex were compared with the effects of stimulating its cutaneous branch, the superficial peroneal nerve (SPN), in two groups of subjects--normals and patients with spinal spasticity subsequent to a clinically complete transection of the spinal cord. Condition-test delays of 20 msec to 2 sec, measured from the end of the 20 msec train (3 pulses at 100 Hz), were investigated. In normal subjects, CPN stimulation at 1.4 X MT profoundly depressed the soleus H-reflex. There was an initial depression (peak 40-90 msec) followed by a slow recovery which was incomplete at condition-test delays of 2 sec. One-half of the subjects showed a late facilitation, or disinhibition, peaking at 170-190 msec. The inhibitory effects were attributed to activation of low threshold, groups I and II, muscle afferents because stimulation of the SPN, at 1.5 X threshold for a compound action potential recorded from the CPN, had only facilitatory effects on the soleus H-reflex. Facilitation occurred at condition-test delays of 30-190 msec. The cutaneous stimulation was presumed to activate the largest, A beta, cutaneous afferents as it elicited a weak paraesthesia on the dorsum of the foot. The results suggested that cutaneous afferents may have contributed to the late facilitation seen with CPN conditioning stimulation. In spinal cord-lesioned subjects, CPN stimulation depressed the soleus H-reflex but the decrease was less and the recovery was faster and more complete than in normals. The magnitude of the initial depression at 20-100 msec varied with the severity of the spasticity, subjects with mild spasticity showing less of a depression. Weak cutaneous conditioning stimulation either had no effect or produced a slight depression of the soleus H-reflex, providing clear evidence that transmission in the pathways mediating the facilitatory effects of cutaneous afferents onto extensor motoneuronal pools is depressed in spinal spasticity. This may shift the balance of activity toward the flexor motoneurones, thus favouring the development of, for example, flexor spasms and flexor hypertonia. Since inhibitory effects from cutaneous stimulation are associated with activation of higher threshold afferents in normal man, the present results may reflect a decrease in the threshold for flexor withdrawal reflexes commonly associated with spasticity of spinal origin.
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PMID:Inhibitory and facilitatory effects from the peroneal nerve onto the soleus H-reflex in normal and spinal man. 244 16

In double-blind sequential study, diazepam was compared with the proven antidepressant moclobemide, in patients with atypical depression. Both agents significantly improved depression ratings over eight weeks of treatment. Diazepam was a significantly better antidepressant than moclobemide at four week, although not at eight weeks. All patients ceased diazepam within one year and none reported withdrawal reactions. These data suggest the need to reconsider that benzodiazepines may be antidepressants and to study their possible antidepressant actions.
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PMID:Is diazepam an antidepressant? 236 Sep 38


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