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)

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

This study examined the effects of selective activation of kappa 1-opioid receptors on excitatory transmission in substantia gelatinosa (SG) using intracellular recordings from SG neurons in transverse slices of the young rat lumbar spinal cord. Monosynaptic and polysynaptic excitatory postsynaptic potentials (EPSPs) were evoked by orthodromic electrical stimulation of A delta or C primary afferent fibers in the dorsal root after blocking inhibitory inputs with bicuculline and strychnine, NMDA receptors with D-2-amino-5-phosphonovaleric acid and mu- and delta-opioid receptors with CTAP and ICI 174,864, respectively. Bath application of dynorphin A1-17 or U-69, 593 caused dual modulation of the peak amplitude of presumed monosynaptic AMPA receptor-mediated EPSPs, decreasing synaptic potentials at nanomolar concentrations in a majority of SG cells examined (dynorphin, 63%; U-69,593, 91%), and increasing EPSPs at micromolar concentrations. Only the inhibitory action of dynorphin A1-17 was consistently and completely blocked by norbinaltorphimine (nor-BNI). Since U-69,593 and nor-BNI are selective for the kappa 1-opioid receptors, the depression of EPSPs is likely to be mediated by the kappa1-opioid receptors. Under conditions of blockade of synaptic transmission with TTX and mu-and delta-opioid receptors, dynorphin A1-17 and U-69,593 hyperpolarize most of SG neurons and decrease their membrane input resistance, the finding suggesting that direct interaction of kappa-agonists with a postsynaptic receptor is likely explanation for the inhibition of EPSPs. However, in some SG cells, the inhibition of EPSPs appears to be of presynaptic origin since dynorphin A1-17 and U-69,593 did depress the EPSPs in the absence of changes in passive membrane properties. Rp-cAMPS, a membrane permeant potent competitive inhibitor of cAMP-activated protein kinase, prevented the depressant effect of dynorphin A 1-17. This finding suggested a possibility that dynorphin A1-17, acting through a decrease in intracellular cyclic AMP levels, can reduce the synaptic responses of SG neurons. These results provide the first electrophysiological demonstration that the activation of kappa 1-opioid receptors inhibits AMPA receptor-mediated primary afferent neurotransmission in the substantia gelatinosa of the young rat spinal cord. This effect may mediate the ability of kappa-receptor agonists to produce antinociception.
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PMID:kappa-opioid receptor agonists modulate excitatory transmission in substantia gelatinosa neurons of the rat spinal cord. 747 39

The purpose of this study was to examine the role of beta-adrenergic receptors in an animal model of stress-induced behavioral depression. beta-Adrenergic receptors in several brain regions and leukocytes of rats were determined by receptor binding techniques using 125I-cyanopindolol (cyp) as ligand and propranolol as displacer for total beta-adrenergic receptors, and ICI 86,406 for beta 1- and ICI 118,551 for beta 2-adrenergic receptors. We observed that the maximum number of binding sites (Bmax) and the apparent dissociation constant (Kd) of 125I-cyp binding to total beta-adrenergic receptors were increased in hippocampus of stressed rats with escape deficits (48 h after training) as compared to control rats. This increase was due to an increase in Bmax and Kd of 125I-cyp binding to beta 1-adrenergic receptors but not to beta 2-adrenergic receptors. There was no significant difference in beta 1-adrenergic receptors in cortex and cerebellum or beta 2-adrenergic receptors in hippocampus, cortex, cerebellum, or leukocytes of stressed (48 h after training) rats with escape deficits as compared to control rats. Interestingly, it was observed that beta 1- and beta 2-adrenergic receptors in various brain regions (cortex, cerebellum, and hippocampus) and beta 2-adrenergic receptors in leukocytes of stressed rats (10 days after training) were not significantly different from control rats, although escape deficits were still present. These results suggest that abnormalities in adrenergic neurotransmission are associated with an upregulation of beta 1-adrenergic receptors, which in turn may be involved in the early stages of behavioral deficits caused by uncontrollable shock.
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PMID:Beta-adrenergic receptor subtypes in stress-induced behavioral depression. 766 50

1. ZENECA ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride, formerly ICI D7288) is a novel sino-atrial node function modulator which selectively slows sinus node rate. Its effects on haemodynamic function have been studied in pentobarbitone anaesthetized dogs, in comparison with zatebradine, atenolol and nitrendipine. 2. ZD7288 lowered heart rate in the dose-range 0.02 to 1.0 mg kg-1 i.v. from 152 to 77 beats min-1. Myocardial contractile function (measured as both dPLV/dtmax and right ventricular free wall developed force) decreased along with rate. Stroke volume increased as rate decreased. Cardiac output decreased at doses in excess of 0.2 mg kg-1, i.v. 3. These haemodynamic changes were reversed when heart rate reduction was reversed by atrial pacing and are, therefore, considered to be indirect consequences of heart rate changes induced by ZD7288. 4. The effects of zatebradine paralleled those of ZD7288 (heart rate reduced from 149 to 60.5 beats min-1 over the dose-range 0.02 to 1.0 mg kg-1, i.v.), except that dPLV/dtmax did not decrease with heart rate and increased during arial pacing. 5. Neither ZD7288 nor zatebradine had significant effects on atrio-ventricular conduction at intrinsic heart rates, but both significantly and dose-dependently prolonged the atrio-ventricular conduction interval during atrial pacing at 180 beats min-1. 6. The observed effects of atenolol were commensurate with removal of beta-sympathetic cardiac drive. Atrial pacing was found not to restore the pre-atenolol heamodynamic state completely. 7. Nitrendipine up to 0.2 mg kg- i.v. induced changes indicative of direct vasodilatation accompanied by reflex compensation, followed by cardiac depression at higher doses. Atrial pacing failed to compensate for the effects of vasodilatation, but caused atrio-ventricular conduction block at doses above 0.5mgkg-1, i.v.8.data show ZD7288 has marked heart rate slowing properties and that accompanying haemodynamic changes appear to be secondary to the rate changes, being reversed by atrial pacing even in the continued presence of the drug. Heart rate slowing without depression of contractile function should prove to be of benefit in the treatment of myocardial ischaemia, particularly in the presence of myocardial dysfunction.
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PMID:Haemodynamic actions of a novel sino-atrial node function modulator, ZENECA ZD7288, in the anaesthetized dog: a comparison with zatebradine, atenolol and nitrendipine. 785 50


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