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)

The effects of aging on spreading depression (SD) were investigated in the Mongolian gerbil (G; age range 1.5 to 58 months; N = 35) and in albino rat (R; 2.5 to 24 months; N = 100). Two strains of rats were studied: Wistar (W; N = 35) and Sprague-Dawley (SDAW; N = 65). SDAW rats were divided into two groups: one group was fed a commercial lab chow diet (CD) containing 22% protein (N = 47), and the other was fed a 22% casein diet (CAS; N = 18). SD was elicited on the frontal cortical surface by 1-min application of 2% KCl and its appearance was recorded (ECoG and DC potential) at two points in the parieto-occipital area of the same hemisphere. SD propagation velocity was measured on the basis of the time spent for an SD "wave" to cross the distance between the two recording points. Within the age range studied, older animals displayed significantly lower SD velocities than the younger ones, independent of the species, strain or diet (velocity ranges, in mm/min: G, 2.22-5.99; W, 2.47-4.12; SDAW-CD, 2.32-4.42 and SDAW-CAS, 2.65-4.14). The correlation coefficients between age and SD velocity were: G. -0.78; W, -0.45; SDAW-CD, -0.68 and SDAW-CAS, -0.72 (P < 0.05 in all cases). As a rule, at each time point the gerbils presented higher SD velocities than the rats of the same age. In another set of experiments, in order to test the role of free radicals in SD, 7 gerbils (14-51 months old) and 13 W rats (3-24 months old) were fed a 22% casein diet free of the antioxidant vitamins C and E for 4-6 weeks before the experiments. No correlation was found between age and SD propagation in these animals fed a diet free of vitamins C and E, although gerbils displayed higher SD velocities than age-matched rats (velocities: G, 3.70-5.34; R, 3.25-4.44 mm/min; correlation coefficients: G; -0.39; W, -0/29; P > 0.05). These data indicate that gerbils have higher SD susceptibility than rats of the same age, and that this susceptibility decreases with aging in both species. The lack of correlation between age and SD velocity in the animals fed a diet free of antioxidant vitamins suggests a possible role of free radicals in cortical SD, in accordance with evidence from other laboratories obtained in the isolated retina.
 ...
PMID:Effect of aging on cortical spreading depression. 918 Nov 17

A multicenter, double-blind, controlled study of pivagabine (4-[(2,2-dimethyl-1-oxopropyl)amino]butanoic acid, CAS 69542-93-4, Tonerg) was conducted in 186 female patients (age: 33-79 years) suffering from climacteric syndrome. In these patients, climacteric syndrome was mainly constituted by symptoms of anxiety, often with mild symptoms of depression and sometimes with mild symptoms of cardiac somatization. The enrolled patients were randomized to two treatment groups: the first group was administered pivagabine, 900 mg/d, for 90 days in succession; the second group was administered placebo for the same period. The efficacy of the treatments was assessed by the Hamilton Depression Rating Scale (HDRS) and the Zung's Self-rating Anxiety Scale (SAS) before the start of treatment, after one month and at the end of treatment. At the end of the study, the physicians and the patients were also requested to evaluate the efficacy of the two treatments. Tolerability was evaluated by recording side effects and by assessing the course of arterial blood pressure, of heart rate and of selected laboratory parameters. The study showed that pivagabine was able to reduce symptoms of anxiety and depression. As a consequence, when asked to evaluate the efficacy, the physicians and the patients consistently stated that pivagabine was effective in controlling the symptoms of anxiety, often associated with mild symptoms of depression, that may arise during the climacterium. Furthermore, these results were obtained with a high safety margin, since the few side effects recorded were mild and transient and the laboratory results were normal as well as the physical examination findings.
 ...
PMID:Role of pivagabine in the treatment of climacteric syndrome. 945 Jan 56

The efficacy of a new drug, pivagabine (4-[(2,2-dimethyl-1-oxopropyl)amino]butanoic acid, CAS 69542-93-4, Tonerg), was studied on 100 patients affected by insomnia, associated with mood disorders. The pharmacological treatment with 900 mg/d pivagabine produced a significant improvement in the quality of both sleep and awakening. The results shown in the present study were positive and likely attributable to the inhibitory modulating activity of pivagabine on corticotropin releasing factor secretion, that is considered to be responsible for insomnia associated with anxiety or coexisting anxiety and depression, observed in patients with chronic stress. The recovery of sleep physiological structure provokes a significant reduction in the criteria reported in the Self-rating Anxiety Scale (SAS).
 ...
PMID:Evaluation of the efficacy of pivagabine on insomnia associated with mood disorders. 945 Jan 57

Depression and distress have in common hypercortisolism, a high turn-over of cerebral monoamines and a wide clinical variability. Results of a clinical open trial with pivagabine (4-[(2,2-dimethyl-1-oxopropyl) amino]butanoic acid, CAS 69542-93-4, Tonerg) on 22 young patients affected by dysthymic disorders and on 38 older patients affected by adjustment disorders following different stressors (mourning, retirement and recovery in institutions of assistance) are reported. Oral treatment with 1800 mg pivagabine lasting 30 days showed in both groups a significant improvement of the psychic state with variations from 50 to 80% of the criteria reported in the Hamilton Rating Scale for Depression (HDRS) and for anxiety (HARS) and in the Self-rating Anxiety Scale (SAS). Good tolerance of the drug and the complete absence of serious side effects considerably contributed to the clinical success.
 ...
PMID:Clinical evaluation of the efficacy of pivagabine in the treatment of mood and adjustment disorders. 945 Jan 58

The effects of ranolazine (CAS 95635-55-5, KEG-1295), a novel antianginal drug, on the ST-segment changes induced by coronary ligation, epinephrine, and vasopressin were examined following oral or intraduodenal administration. In anesthetized dogs, intraduodenal administration of KEG-1295 (10, 30, or 50 mg/kg) or atenolol (10 mg/kg) significantly attenuated the ST-T wave elevation induced by 2-min coronary ligation imposed during electrical heart pacing (200 beats/min). This antianginal effect of KEG-1295 persisted for 3 h without any changes in hemodynamic parameters, while that of atenolol was accompanied by more or less maintained decreases in diastolic blood pressure, heart rate, and the maximum first derivative of left ventricular pressure. In anesthetized rats, oral administration of KEG-1295 (10, 30, or 50 mg/kg) attenuated the ST-T wave elevation induced by epinephrine (0.3 microgram/kg i.v.) in a dose-dependent manner, although KEG-1295 (10 or 30 mg/kg p.o.) failed to attenuate the ST-segment depression induced by vasopressin (0.2 IU/kg i.v.). These findings suggest that, taken orally, KEG-1295 may exert potent protective effects against angina pectoris, except that caused by vasospasm. Further, KEG-1295 may be categorized as a new type of antianginal agent, without any primary hemodynamic effects.
 ...
PMID:Antianginal effects of ranolazine in various experimental models of angina. 1021 61

In a randomised double-blind comparative trial, the antidepressant efficacy of a daily dose of 800 mg of the St. John's wort extract LoHyp-57 (dry extract of St. John's wort, drug extrakt ratio 5-7:1, solvent, ethanol 60% [w/w]) was shown to be equivalent to that of 20 mg fluoxetine (CAS 54910-89-3) in elderly patients with mild or moderate depressive episodes according to ICD 10 (International Statistical Classification of Diseases and Related Health Problems). Treatment was given for six weeks. 149 out-patients (129 females and 20 males) were included in the intention-to-treat analysis. 72 of these patients were assigned to the ICD 10 diagnostic criterion F32.0 (mild depressive episode), while 77 patients were suffering from moderate depressive episodes, corresponding to F32.1. The principal target criterion was the patient's global score on the HAMILTON Depression Scale (items 1-17). During the six-week course of treatment with LoHyp-57, the HAMILTON global score fell from 16.60 points at entry to 7.91 points, and in the fluoxetine sample it fell from 17.18 to 8.11 points. In the group of patients with mild depressive episodes, the score showed a mean fall from 14.21 to 6.21 points on LoHyp-57, and from 15.21 to 7.46 points on fluoxetine. In patients with moderate depressive episodes, the score showed a mean fall from 18.73 to 9.43 points on LoHyp-57 and from 19.10 to 8.75 points on fluoxetine. The efficacy of both medications was found to be equivalent both in mild and moderate depressive episodes. Both treatment groups showed adverse drug reactions (ADRs). Twelve ADRs with a possible relationship to the study medication were reported during treatment with LoHyp-57. Six patients were prematurely withdrawn from treatment with the study medication for this reason. On fluoxetine 17 ADRs occurred with a possible relationship to the study medication. These led to abandonment of treatment and therefore premature withdrawal from the study in 8 cases.
 ...
PMID:Comparison of equivalence between the St. John's wort extract LoHyp-57 and fluoxetine. 1033 46

The class III antiarrhythmic azimilide (E-1-[[[5-(4-chlorophenyl)-2-furanyl]methylene]-amino]-3-[4-(4-methyl-1- piperazinyl)butyl]-2,4-imidazolidinedione dihydrochloride; WHO No. 7299, CAS 149888-94-8), by slow infusion or stepwise bolus doses, was evaluated for effects on heart rate, blood pressure, and cardiac pump function, excitability, and refractoriness in anesthetized dogs. Infusion (0.6 mg/kg/min) in male beagles (n = 5) to a maximum dose of 54 mg/kg increased QTc more than 20 ms at 2.0 mg/kg. At a dose of 8.9 mg/kg i.v., QTc increased 34% above baseline and remained elevated throughout the subsequent infusion and for at least 60 min postinfusion. At this maximum class III dose, azimilide increased heart contractile force (HCF) 10% and +dP/dt 34% and decreased heart rate (HR) 12%, without significantly changing mean blood pressure (MBP), left ventricular end diastolic pressure, -dP/dt, stroke volume (SV), or cardiac output (CO). At the mean maximum 47 mg/kg i.v. dose, QTc remained elevated, but decreases were observed in HCF (-27%), +dP/dt (-24%), -dP/dt (-35%), SV (-16%), and CO (-52%). Cumulative intravenous bolus injections of azimilide (0.3, 1, 3, 10, and 30 mg/kg) in male mongrels (n = 5) increased effective refractory period (ERP) and +dP/dt (18% and 16%, respectively, at 10 mg/kg) as a function of dose and significantly decreased HR (-22% at 10 mg/kg). MBP decreased significantly (-23%) only at the highest dose. Ventricular fibrillation threshold (VFT) was unchanged at 30 mg/kg. Effects of dl- (n = 3) and d-sotalol (n = 4) on ERP and HR were similar to azimilide's, but both compounds caused a greater MBP depression and VFT elevation. These results suggest that azimilide is well tolerated by the cardiovascular system, providing an increase in contractility and a slight decrease in HR at intravenous doses that produced a large or maximum increase in cardiac refractoriness.
 ...
PMID:Effects of intravenous azimilide on cardiac performance, fibrillation threshold, and hemodynamics in anesthetized dogs. 1096 15

It is well accepted that long-term administration of opioids results in a dose-related constipation. No data so far have demonstrated conclusively whether such constipation is also seen after intake of a controlled release formulation. It was therefore of interest to evaluate whether increasing doses of a controlled release formulation of dihydrocodeine (DHC, CAS 125-28-0) after oral administration also induces a dose-related increase in constipation. Additionally, it was of interest to study whether such a peripheral opioid-related side effect is also seen in another, central receptor-mediated effect, the constriction of the pupil, at clinically relevant doses. Twelve volunteers were given controlled release DHC (60 and 120 mg, respectively) or placebo orally within a randomized, double-blind cross-over study. In order to determine the degree of constipation, oro-cecal transit time was measured using the H2-exhalation test. Additionally, in order to evaluate a centrally mediated effect, the response of the pupil to light was quantified using the pupillary light reflex technique. Both, peripherally and centrally mediated effects were compared to placebo. DHC at both dosages induced a significant (p < 0.01) prolongation of oro-cecal transit time when compared to placebo. However, prolongation of oro-cecal transit was not significantly longer when comparing the lower (60 mg) with the higher dose (120 mg). DHC also induced a significant (p < 0.005) depression of the pupillary light reflex from 53.9 mm (control) to 8.3 and 7.4 mm, respectively. Similar to intestinal transit, the pupillary light reflex was not significantly different among the two doses of DHC. Also, both dosages induced a similar amount of side effects. Tiredness and dry mouth were reported in 80% after both doses while vertigo was reported in 5% and 1% complained of headache. None of the volunteers reported nausea or emesis. It is concluded that opioid receptor sites, which are located in the plexus myentericus of the intestinal wall, are responsible for the delay in propulsion. Because of the controlled release of a fixed amount of DHC over time there is constant binding of the ligand followed by a constant conformational change of peripheral and central receptor sites. Thus constant release induces no dose-related increase in oro-cecal transit and inhibition of the pupillary light reflex.
 ...
PMID:Dose-related effects of controlled release dihydrocodeine on oro-cecal transit and pupillary light reflex. A study in human volunteers. 1121 27

We have characterized desloratadine (5H-benzo[5,6]cyclohepta[1,2-b]pyridine, 8-chloro-6,11-dihydro-11-(4-piperidinylidene), CAS 100643-71-8) as a potent antagonist of the human histamine H(1) receptor. [3H]Desloratadine bound to membranes expressing the recombinant human histamine H(1) receptor in Chinese hamster ovary cells (CHO-H(1)) in a specific and saturable manner with a K(d) of 1.1+/-0.2 nM, a B(max) of 7.9+/-2.0 pmol/mg protein, and an association rate constant of 0.011 nM(-1) x min(-1). The K(d) calculated from the kinetic measurements was 1.5 nM. Dissociation of [3H]desloratadine from the human histamine H(1) receptor was slow, with only 37% of the binding reversed at 6 h in the presence of 5 microM unlabeled desloratadine. Seventeen histamine H(1)-receptor antagonists were evaluated in competition-binding studies. Desloratadine had a K(i) of 0.9+/-0.1 nM in these competition studies. In CHO-H(1) cells, histamine stimulation resulted in a concentration-dependent increase in [Ca(2+)](i) with an EC(50) of 170+/-30 nM. After a 90-min preincubation with desloratadine, the histamine-stimulated increase in [Ca(2+)](i) was shifted to the right, with a depression of the maximal response at higher concentrations of antagonist. The apparent K(b) value was 0.2+/-0.14 nM with a slope of 1.6+/-0.1. The slow dissociation from the receptor and noncompetitive antagonism suggests that desloratadine may be a pseudoirreversible antagonist of the human histamine H(1) receptor. The mechanism of desloratadine antagonism of the human histamine H(1) receptor may help to explain the high potency and 24-h duration of action observed in clinical studies.
 ...
PMID:Biochemical characterization of desloratadine, a potent antagonist of the human histamine H(1) receptor. 1216 64

The reproductive toxicity of gamma-ethyl-gamma-phenyl-butyrolactone (EPBL, CAS 53380-21-5), a new anticonvulsant and hypnotic drug, was investigated by performing fertility and peri- and post-natal studies in mice. In both studies, EPBL was administered by gavage at 0, 50, 10, or 200 mg/kg doses. The first study found parent toxicity as measured by reduced body weight at the higher dose. At the same dose, the number of live fetuses was decreased. However, neither male or female fertility nor the reproductive performance of mice were affected. The results of the second study showed that the only negative effects were a depression of maternal weight gain and a decrease in body weight of the litter at birth which was 200 mg/kg. A reduction in the survival rate was also seen. There was no evidence that treatment of F0 females from day 15 of pregnancy to day 21 post-partum affected either the reproductive capacity of the F1 offspring or the development of F2 progenies. The non observed effects levels (NOEL) for both studies can be estimated at 100 mg/kg.
 ...
PMID:Reproductive toxicity of gamma-ethyl-gamma-phenyl-butyrolactone, a new anticonvulsant and hypnotic drug, in mice. Fertility and peri- and post-natal studies. 1218 75


<< Previous 1 2 3 4 5 Next >>