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)

A double-blind controlled study of the effect of piperazine estrone sulfate on sleep, depression, anxiety, and hot flushes was conducted in 34 perimenopausal women aged 45-55. 1/2 of the group received placebo for 6 weeks, then piperazine estrone sulfate (1.5 mg twice daily) for 8 weeks, while 1/2 remained on placebo throughout. Sleep was recorded electrophysiologically every week after adaptation and baseline readings. Mood and anxiety were rated daily by means of visual analogue scales. Hot flushes were counted daily. Observer rating scales of anxiety and depression were completed at the beginning and end of the baseline placebo period and at the end of the 1st and 2nd treatment month. During the 1st month of active treatment, the amount of intervening wakefulness in the first 6 hours of sleep decreased significantly more in the estrone group than in those on placebo. Between the baseline period and the 2nd treatment month, the estrone group showed a significantly greater decrease in the total amount of wakefulness and in the frequency of awakenings. Their total amount of rapid eye movement sleep increased. Mood and anxiety improved and the number of hot flushes decreased to a similar degree in both groups.
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PMID:Effect of oestrogen on the sleep, mood, and anxiety of menopausal women. 33 4

For assessment of the effect of trihexiphenidil on the excitability state of the alpha-motoneurons of the plantar flexor of the foot in patients with drug-induced parkinsonian rigidity curves of the excitability of motoneurons of the soleus muscle were plotted in two variants of experiments: I. with afferent stimulation of the Ia fibres of the soleus muscle as the conditioning and testing stimulus (tibial nerve in the popliteal fossa), II. with afferent stimulation of Ia fibres of the anterior tibial muscle (peroneal nerve behind the fibular capitulum) used as the conditioning stimulus and stimulation of the tibial nerve as the testing stimulus. These investigations were carried out on 12 psychiatric patients who received no drugs at the time of these investigations (control group), 13 similar patients treated with chlorpromazine, 12 treated with phenothiazine compounds with piperazine ring in the side chain. The investigations were repeated 30-50 min. after oral administration of trihexiphenidil 5 mg. In variant I typical excitability curves were obtained and 5 phases could be discerned in them. In patients treated with piperazine-containing phenothiazine derivatives inducting more significant parkinsonian effects phase III - depression - was significantly shortened, and the excitability was raised in phase IV. In variant II phases III and IV were reversed and in phase IV a rise in excitability was observed in place of depression. In variant II in the group of drug-induced parkinsonism as compared with controls the rise in exictability was greater in phase III and depression in phase IV was smaller. The effect of trihexiphenidil in variant I depended on the initial state. In controls and in patients treated with chlorpromazine trihexiphenidil reduced the duration of phase III of depression and decreased its intensity. In atients treated with phenothiazines containing the piperazine ring depression in phase III was weak but increased after trihexiphenidil administration and increased excitability in phase IV was decreased. The curves became similar to those obtained in controls. In variant II in the control group excitability in phase III increased after trihexiphenidil administration.
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PMID:[Effect of trihexphenidyl on the excitability of alpha motor neurons of the foot plantar flexor in chemically induced parkinsoniam rigidity]. 112 50

Ranolazine (RS 43285) is a new piperazine derivative with anti-ischemic properties attributed to a modulation of myocardial metabolism. Its antianginal action was assessed in 104 patients recruited in a double-blind, crossover, randomized study comparing placebo with a single dose of ranolazine (10, 60, 120, and 240 mg). All patients had chronic stable angina pectoris and remained symptomatic (at least 0.1 mV ST-segment depression and angina during prestudy exercise testing) despite treatment with a beta-blocker or with diltiazem. No significant effects of ranolazine on exercise duration or time to angina were observed after the dose of 10, 60, and 120 mg. After the 240 mg dose, however, significant improvement in exercise duration (+13.1% in the combined group, two-tailed p = 0.002; +14.3% in the beta-blocker group, p = 0.009; +11.9% in the diltiazem group, p = 0.06), in time to angina (+56.8 s, p = 0.008), and in time to 1 mm ST-segment depression was observed. The cumulative proportion of patients who improved their time to angina by at least 30 s above placebo were 25, 42, 50, and 72% with the doses of 10, 60, 120, and 240 mg, respectively. Sixty-seven percent of the patients with ranolazine plasma levels above 500 ng/ml improved their time to angina against 40% at plasma levels below 500 ng/ml and summed ST-segment depression during exercise and recovery was also significantly reduced at these plasma concentrations. Both heart rate and arterial pressure at rest and at peak exercise were unchanged after ranolazine, 240 mg.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of a new metabolic modulator, ranolazine, on exercise tolerance in angina pectoris patients treated with beta-blocker or diltiazem. 138 22

The 5-HT1A agonists buspirone, gepirone and ipsapirone have been shown to possess antidepressive-like properties in several animal models of depression as well as in clinical studies. These compounds are metabolized to 1-(2-pyrimidinyl)-piperazine (1-PP) in rats and humans. In the learned helplessness paradigm, buspirone exhibits a biphasic action: at low or moderate doses it shows an antidepressant-like effect but this action progressively disappears as the doses are increased. In order to establish whether 1-PP affects the reversal of helpless behaviour induced by the 5-HT1A agonists at high doses in rats, we have investigated its role in the learned helplessness. Thus, 1-PP has been evaluated alone (0.06-4 mg/kg/day) or in combination with a selective 5-HT1A agonist 8-OH-DPAT (0.25 mg/kg/day) which is not metabolized to 1-PP and buspirone (0.5 mg/kg/day). In addition, buspirone at a higher dose (2 mg/kg/day) has also been examined in the presence of proadifen which inhibits oxidative metabolism. Our results show that i) daily injections of 1-PP did not reverse helpless behaviour, ii) the reversal of helpless behaviour by 8-OH-DPAT or active dose of buspirone was antagonized by daily coadministration of 1-PP, iii) in rats pretreated with proadifen, the highest "inactive" dose of buspirone induces a reversal of helpless behaviour. These results strongly suggest that up to a certain concentration 1-PP can impair the effects of the parent drug in the learned helplessness.
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PMID:1-(2-pyrimidinyl)-piperazine may alter the effects of the 5-HT1A agonist in the learned helplessness paradigm in rats. 167 95

A 10-min bilateral carotid occlusion (BCO) in Mongolian gerbils induces transient generalized epileptic discharges in the hippocampal and cortical regions, which are followed by long lasting interictal spiking activity. An initial peak of this activity occurs within 18-36 h after BCO, then it decreases slowly and completely disappears by the 6th-7th day. On the 7th day, morphological evidence shows a selective loss of CA1 hippocampal neurons. 4-(3-Phosphonopropyl)-2-piperazine-carboxylic acid (CPP), a competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor was administered (7 or 15 mg/kg i.p.) immediately after clamping, and again every 12 h for 3 consecutive days. It induced a dose-related depression of epileptic activity, while, on the other hand, at both dosages, it always prevented the loss of CA1 neurons. The results are discussed in view of the different mechanisms mediating cell damage and epileptic activity.
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PMID:Epileptic activity following cerebral ischemia in Mongolian gerbils is depressed by CPP, a competitive antagonist of the N-methyl-D-aspartate receptor. 183 55

1. Monosynaptic (MSR) and polysynaptic (PSR) segmental reflex responses were recorded from a ventral root of the neonate rat hemisected spinal cord. Amplitudes of the two components were monitored with a peak height detector. 2. 5-Hydroxytryptamine (5-HT) depressed the MSR and PSR in a concentration-dependent manner. The IC50 for MSR depression was 9.5 +/- 3.2 microM and for PSR depression was 9.0 +/- 4.8 microM. 3. Blockade of neuronal uptake of 5-HT by citalopram (0.1 microM) greatly increased sensitivity to 5-HT. In the presence of citalopram, the IC50 for MSR depression was 30 +/- 18 nM and for PSR depression was 89 +/- 23 nM. 4. 5-HT did not depress the MSR or the PSR by releasing glycine since strychnine (1 microM) did not prevent these actions of 5-HT. 5. 5-Carboxamidotryptamine (5-CT), 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), RU 24969, 1-[3-(trifluoromethyl)phenyl]-piperazine (TFMPP) and methysergide were full agonists for depression of the MSR. The IC50 for 5-CT was 3.6 +/- 0.5 nM, for 8-OH-DPAT was 0.4 +/- 0.04 microM, for TFMPP was 0.93 +/- 0.3 microM and for methysergide was 21.8 +/- 3.0 nM. The order of potency was 5-CT greater than methysergide greater than 5-HT greater than 8-OH-DPAT greater than TFMPP. 6. 8-OH-DPAT, RU 24969, TFMPP and methysergide had either no or only a minor action in reducing the PSR. 5-CT caused a 50% depression at the highest concentration tested (30 nM). 7. Neither ketanserin (1 microM) nor spiperone (1 microM) caused appreciable blockade of 5-HT depression of the MSR or 5-HT depression of the PSR. 8. Blockers of neuronal 5-HT uptake (citalopram 0.1 or 1 microM, fluvoxamine 1 microM) usually reduced the MSR and, to a lesser extent, the PSR. Reflex depressions were reversed by ketanserin (1 microM). 9. It was concluded that 5-HT has a potent depressant action on segmental reflexes; depression of the MSR is unrelated to depolarization of motoneurones. Although depression of the MSR was mimicked by 5-HTIA receptor ligands, the action of endogenous 5-HT may be mediated through 5-HT2 receptors. Exogenous 5-HT may act at a mixture of 5-HT receptor subtypes to depress the MSR.
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PMID:Inhibition of reflex responses of neonate rat lumbar spinal cord by 5-hydroxytryptamine. 193 39

The influence of alpha 2-adrenoceptor blockade on the activity of desipramine in an experimental model of depression was studied by using idazoxan and 1-(pyrimidinyl)piperazine (1-PP). The two drugs antagonists at these receptors, were studied for their ability to modify the effect of repeated treatment with the antidepressant, desipramine in the forced swimming test. Idazoxan (0.03, 0.3 and 3 mg/kg s.c.) and 1-PP (0.3 and 3 mg/kg p.o.) given with the last dose of a 7-day schedule of 10 mg/kg i.p. desipramine significantly reduced the effect of the latter on immobility. On its own neither drug modified the immobility time of rats at any dose. Infusion of various concentrations of idazoxan (1.6, 8 and 40 ng/microliters) in the rat locus coeruleus (LC), dose dependently antagonized the effect of desipramine without causing any appreciable change in motor behavior or immobility. The effect of idazoxan (8 ng/microliters) infusion in the LC was completely prevented by administering 6 micrograms 6-hydroxydopamine in the same region 12 days earlier. It thus appears that alpha 2-adrenoceptor blockade prevents the effect of desipramine in the forced swimming test, presumably by an effect on noradrenaline-containing cells in the LC. The question of how blockade or activation of alpha 2-adrenoceptors, both in the LC and in other sites, could influence antidepressant activity is discussed.
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PMID:Alpha 2-adrenoceptor blockade prevents the effect of desipramine in the forced swimming test. 196 1

A range of agonists and antagonists active at different glutamate/aspartate (Glu/Asp) receptor subtypes were injected into rat ventral tegmental (VTA) sites downstream from self-stimulation electrodes in the medial forebrain bundle. Control injections were made into the contralateral tegmentum. Variable-interval (VI 10 s) self-stimulation was not significantly affected by a specific antagonist of N-methyl-D-aspartate (NMDA)-type receptors (D,L-2-amino-5-phosphonovaleric acid (2-AP5), 10 and 50 nmol). Broad-spectrum excitatory amino acid (EAA) antagonists viz cis-2,3-piperidine dicarboxylate (cPDA) (10 and 50 nmol), gamma-D-glutamylaminomethyl sulphonic acid (GAMS) (10 nmol) and p-chlorobenzoyl-2,3-piperazine dicarboxylic acid (pCB PzDA) (2.0 and 10 nmol), active at kainate, quisqualate, as well as NMDA receptors, all produced significant depression of responding when injected into the ipsilateral, but not the contralateral, tegmentum. Compounds inhibiting Glu/Asp reuptake had variable effects: strong depression with dihydrokainic acid (7.5 nmol), or no significant effect (L-threo-3-hydroxyaspartic acid, 2.0 and 10 nmol). The receptor agonist, NMDA (10 nmol), depressed responding regardless of injection side; kainic and responding regardless of injection side; kainic and quisqualic acid elicited myoclonic and other non-specific responses in preliminary tests, and were not examined further; enhanced responding was not seen. The side-specific blockade of responding by non-NMDA antagonists indicates the existence of non-NMDA EAA terminals in the VTA, signalling the receipt of hypothalamic brain-stimulation reward. Caudally directed EAA projections terminating on A10 dopamine cell bodies may account for depression of self-stimulation by EAA antagonists.
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PMID:Excitatory amino acid pathways in brain-stimulation reward. 197 79

Lidoflazine, a piperazine derivative calcium antagonist, was investigated as therapy in 22 patients with microvascular angina (chest pain, angiographically normal coronary arteries and left ventricle, microvascular constrictor response to pacing after ergonovine administration and limited coronary flow response to dipyridamole). Eighteen of 22 patients reported symptom benefit while taking lidoflazine 360 mg daily. Compared to baseline exercise treadmill testing, lidoflazine resulted in significant improvement in exercise duration (812 +/- 337 vs 628 +/- 357 seconds, p less than 0.01) and time to onset of chest pain (530 +/- 343 vs 348 +/- 246 seconds, p less than 0.01). The 5 patients with ischemic ST-segment changes during baseline testing demonstrated an almost 4-minute delay in ST-segment depression (3 patients) or no ST-segment depression (2 patients) while taking lidoflazine. Repeat invasive study of coronary flow in 11 patients taking lidoflazine demonstrated significantly greater coronary vasodilation at rest, during pacing, during pacing after ergonovine and after dipyridamole administration (all p less than 0.03), compared to the initial drug-free study. During the randomized, placebo-controlled phase of the study with 7-week treatment periods, 9 of 11 patients who completed this phase of the study preferred lidoflazine and all demonstrated improved exercise capacity with lidoflazine compared to placebo. However, 3 patients developed malignant ventricular arrhythmias, and 1 died while taking lidoflazine, resulting in termination of the study. Limited coronary vasodilator response in microvascular angina has a reversible vasoconstrictor component and may be due to elevated systolic calcium levels. Despite the hemodynamic, symptom and exercise benefit, lidoflazine may be unsafe for clinical use because of its propensity to cause potentially fatal ventricular arrhythmias.
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PMID:Beneficial and detrimental effects of lidoflazine in microvascular angina. 219 96

Obsessive-compulsive disorder (OCD) is emerging very clearly as a serotonin specific illness. The evidence for this comes from a variety of clinical sources. Firstly the efficacy of 5-HT uptake inhibitors, especially clomipramine, is consistent and strong. Secondly clomipramine has not merely been found to be effective against placebo in 9 placebo controlled studies, it is also found to be more effective in some studies than reference tricyclic antidepressants and monoamine oxidase inhibitors. In other studies tricyclic antidepressants do not appear to be better than placebo. The lack of efficacy of general antidepressants, neuroleptics and benzodiazepines supports the specificity of the serotonin effect. Thirdly the evidence of the efficacy of clomipramine in OCD without concomitant depression reported by Montgomery 1980 and supported by other studies suggests that 5-HT uptake inhibitors have a specifically anti-obsessional effect. The lack of response of depressive symptoms in OCD to other antidepressants suggests that these depressive symptoms are integral to OCD and will only respond when the OCD is treated. Many of the studies found efficacy for 5-HT uptake inhibitors compared with placebo despite both groups being treated with concomitant behaviour therapy. This argues either for behaviour therapy being relatively ineffective or for there being a synergistic effect with the 5-HT uptake inhibitor which is more likely. Results from studies with selective serotonergic probes with a worsening of OCD symptoms in response to the 5-HT1A agonist, m-chlorophenyl piperazine, add support to the serotonergic hypothesis of OCD but further investigation is needed.
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PMID:[Biological treatments in obsessive-compulsive disorder]. 220 92


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