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)

To investigate the mechanism of action of ECT in depression, functional changes in central noradrenergic systems, resulting from a series of electroshock- or photic-induced seizures have been evaluated in baboons. The plasma growth hormone (GH) response to IV infusion of an alpha 2-noradrenergic agonist clonidine (0.02 mg/kg) or a beta 2-adrenergic antagonist, ICI 118,551 (0.02 mg/kg) has been measured before, during and up to 15 days after the series of seizures. Electroshock (ECS) or sham ECS was given with standard clinical premedication (atropine, methohexital, suxamethonium and oxygen ventilation) seven times over 15 days. Plasma GH responses were unchanged 24 h after one or seven ECS. An enhanced GH response occurred 7 and 15 days after the seventh ECS. Sham ECS (seven times in 15 days) produced no changes in GH response to clonidine. The plasma GH response to ICI 118,551 was apparently decreased 1 and 7 days after the seventh ECS. Photic seizures were induced seven times in 15 days in baboons which were primed with a subconvulsant dose of D,L-allylglycine (180 mg/kg), but were otherwise drug-free. Plasma GH responses to clonidine were enhanced 1 and 7 days after the seventh photically induced seizure. It is concluded that in the primate there is an enhancement of a central alpha 2-noradrenergic response during 1-15 days after a sequence of generalised seizures. The time course of this enhancement appears to be influenced by drugs given directly before the seizures.
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PMID:Changes in noradrenergic neuroendocrine responses following repeated seizures and the mechanism of action of ECT. 612 99

We examined the interaction between isoproterenol and erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol (ICI 118,551), a beta-2 selective adrenergic receptor antagonist, with respect to heart rate, diastolic blood pressure and twitch tension (soleus muscle) in anesthetized cats. Dose-response curves to isoproterenol (0.025-1.0 micrograms/kg i.v.) were generated for each parameter and then repeated successively after three doses of ICI 118,551 (10, 25 and 100 micrograms/kg i.v.) ICI 118,551 did not significantly alter isoproterenol-induced changes in heart rate, but effects on diastolic blood pressure and twitch tension were inhibited competitively. The data confirm the beta-2 nature of the skeletal muscle adrenergic receptor and suggest that it may be slightly more sensitive than that in blood vessels. Because depression of twitch tension is known to correlate with essential tremor, the data are consistent with clinical reports demonstrating control of tremor by nonselective beta adrenergic receptor antagonists. ICI 118,551 may be efficacious in controlling tremor in man.
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PMID:The effects of a beta-2 selective adrenergic receptor antagonist (ICI 118,551) on twitch tension in cat soleus muscle. 612 19

ICI 89,406, a new cardioselective beta-adrenoceptor antagonist possessing marked intrinsic sympathomimetic activity, was administered (0.04 mg/kg, i.v.) to 10 patients with stable, uncomplicated, exercise-induced angina pectoris and angiographically proven coronary artery disease. The drug resulted in a significant reduction in heart rate (from 125 +/- 5 to 110 +/- 4/min, p less than 0.001), mean systemic arterial pressure (from 147 +/- 4 to 137 +/- 3 mm Hg, p less than 0.01), and electrocardiographic ST-segment depression (from 1.9 +/- 0.5 to 0.8 +/- 0.3 mm, p less than 0.01) without any change in pulmonary arterial or wedge pressure during submaximal supine leg exercise on a bicycle ergometer. These changes were accompanied by a reduction of cardiac output in 6/10 patients and of the duration of pain in 8/10 patients. At rest, all the hemodynamic parameters remained essentially unchanged in comparison with the control study. These studies indicate that ICI 89,406 produces effective beta-adrenoceptor blockade during exercise in patients with angina pectoris. The partial agonist activity of the drug may be responsible for the minimal circulatory response at rest.
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PMID:Clinical, electrocardiographic, and hemodynamic effects of ICI 89,406, a new cardioselective beta-adrenoceptor antagonist with intrinsic sympathomimetic activity, in patients with angina pectoris. 615 41

1. Cyclic AMP levels have been determined in the soleus muscles of anaesthetized cats in the absence of drugs, and during depression of incomplete tetanic contractions produced by (-)-isoprenaline, ICI 63,197 (a phosphodiesterase inhibitor) or levodopa. 2. Cyclic AMP levels were elevated at the peak of tension depression produced by isoprenaline. Effects of isoprenaline on cyclic AMP and on contractions were dose dependent and statistically significantly related one to the other. Both effects were blocked by propranolol. 3. ICI 63,197 and levodopa produced isoprenaline-like effects on contractions but times to peak effect and recovery were longer. Cyclic AMP levels estimated during the depressant action were elevated. 4. The results support the involvement of cyclic AMP in the depressant effect of beta-adrenoreceptor agonists on slow-contracting mammalian skeletal muscle.
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PMID:Effects of isoprenaline, levodopa and a phosphodiesterase inhibitor (ICI 63,197) on cyclic AMP levels and contractions of soleus muscles in anesthetized cats. 625 31

In an effort to identify delta-receptor-specific properties for opioid modulation of seizure activity, studies were conducted with ICI 154,129, a putative delta-receptor antagonist, in the rat flurothyl test. Rats were pretreated i.c.v. with ICI 154,129 (50 micrograms) which, at this dose, does not alter normal seizure thresholds. Mean seizure thresholds for control groups (i.c.v. saline) ranged between 323-349 sec. In this test, D-Ala2-D-Leu5 enkephalin (20 micrograms, i.c.v.), metkephamid (40 mg/kg, s.c.), and etorphine (20 micrograms/kg, s.c.) raised seizure thresholds by 117, 128, and 140% of control, respectively. Meperidine (25 mg/kg, s.c.) lowered seizure thresholds by 14% less than control. Pretreatment with ICI 154,129 failed to antagonize the proconvulsant action of meperidine or the anticonvulsant and behavioral depressant actions of etorphine. The increases in seizure threshold produced by DADL and metkephamid (two delta-directed ligands) were significantly attenuated by ICI 154,129. However, the DADL-induced wet-shakes, rigid immobility, and behavioral depression were insensitive to ICI 154,129. These data indicate that ICI 154,129 possesses delta-receptor antagonistic properties in this in vivo model of seizure activity. Furthermore, since only the changes in seizure threshold were antagonized, it may be inferred that opioid-induced behavioral depression and DADLE wet-shakes are not a function of delta-receptor activity.
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PMID:A selective role for delta-receptors in the regulation of opioid-induced changes in seizure threshold. 631 16

In order to avoid Cremophor-related reactions and reduce the incidence of pain on injection, diisopropylphenol (ICI 35,868; propofol) has been reformulated as an emulsion. One hundred and fifteen patients received an induction dose of propofol in the new formulation. The dose required to induce anaesthesia in 95% of healthy, unpremedicated patients was 2.5 mg/kg. Induction was associated with a degree of cardiovascular and respiratory depression. There were no adverse reactions although there were a number of minor side-effects. The incidence of pain on injection was low (3%) and the overall quality of induction was assessed as good or adequate in 92% of patients.
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PMID:Dose requirements of ICI 35,868 (propofol, 'Diprivan') in a new formulation for induction of anaesthesia. 633 3

The activity of a new i.v. anesthetic agent ICI 35 868, a compound unrelated to currently used barbiturate, eugenol or steroid agents, has been examined in a range of animal species. Some of the properties of ICI 35 868 resemble those of thiopentone in that it is a rapidly acting agent which produces anaesthesia of short duration and without excitatory side-effects. Both agents have a similar therapeutic index and produce equivalent cardiovascular and respiratory effects. In the mouse ICI 35 868 is 1.8 times more potent than thiopentone as a hypnotic. However, the anaesthetic profile of ICI 35 868 differs from that of thiopentone in that recovery is rapid following repeated administration, no tissue damage is produced by perivascular or intra-arterial injection and greater reflex depression and more profound e.e.g. changes are produced at equipotent doses. This new agent has been shown to be compatible with a wide range of drugs used for preanaesthetic medication, inhalation anaesthetics, and neuromuscular blocking drugs.
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PMID:Animal studies of the anaesthetic activity of ICI 35 868. 677 50

276 ambulatory depressed patients were entered into a multicentered clinical study to assess the effectiveness and acceptability of viloxazine. Results from global assessment by the trialist showed that viloxazine monotherapy produced a good response in 83% of patients. Improvement has been seen in all grades of depression including the sad-depressed, inhibited-apathetic and masked-depressed syndrome. Only 38 patients did not improve on viloxazine and even including 46 withdrawals because of insufficient efficacy and/or side-effects, the clinical response with viloxazine exceeded by far the rate of spontaneous remission expected in depressive illness, thus reducing a major objection against open studies like this. This study also confirmed the rapid onset of drug effect; since as early as after 1 week of treatment, statistically significant improvements were seen even in severe forms of depression. As to the unwanted effects of therapy, viloxazine was again favourably assessed by trialists. Nausea and vomiting were the main side-effects reported and accounted for withdrawal in 8% of the original 276 patients. As expected from previous findings no change in cardiovascular function was observed. So it can be concluded from this open trial, that VIVALAN ICI is an effective antidepressant for use in out-patients. It produces a fairly rapid onset of action and has been generally well tolerated.
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PMID:Viloxazine (Vivalan ICI) in depression: results of a field trial of 276 patients in neuropsychiatric practice. 704 60

In a double blind trial in 88 patients, 71 of whom were included in the fin al evaluation, viloxazine (Vivalan ICI) showed an effectiveness corresponding to imipramine. Both antidepressives show properties for lysis of depression and improvement of mood, the target symptom is vitally depressive disturbance of mood. There was clear improvement of depression, anxieties, restlessness, loss of initiative and activity as well as pain syndromes in psychosomatic disorders. In cases of psychomotor inhibition viloxazine was superior to the older drug. Effectiveness of viloxazine commenced rapidly as demonstrated by control assessment after 10-14 days. Results improved further in a second equally long treatment period. Tolerance of viloxazine was superior to imipramine.
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PMID:[Double blind comparison of the antidepressives viloxazine and imipramine (author's transl)]. 707 79

In 103 out of 220 alcoholics (46.8%) with no heart disease electrocardiographic abnormalities were found, sinus tachycardia, T-wave irregularities and intraventricular conduction disturbances being the most common features. Comparing 138 chronic alcoholics with those of 134 healthy abstainers for the systolic time-intervals, the following abnormalities were found in the former group: prolonged PEP and ICT, shortened LVET, increased PEP/LVET and heart rate. Correction of the time intervals for heart-rate left the direction of the changes unaffected. Nor was the age of the subjects found to affect the intervals to any significant degree either in the alcoholics or in the control group. It is therefore assumed that the effect of alcohol on the time-intervals operates through at least two mechanisms, an increase in heart-rate, and a depression of myocardial contractility.
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PMID:Changes in cardiac function in the "preclinical" stage of alcoholic heart disease. 745 29


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