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)

Previous work in this laboratory has suggested that antagonist action of 5-hydroxytryptamine2 (5-HT2) receptors and agonist action of 5-HT1 receptors results in antidepressant-like effects (increased reinforcement rate and decreased response rate) in rats performing under the differential-reinforcement-of-low-rate 72-sec schedule (DRL 72-s) of reinforcement. Serotonergic mediation of antidepressant drug effects on DRL 72-s behavior was assessed with a series of 5-HT agonists, and blockade of the effects of the antidepressant drugs clorgyline and fluoxetine (which presumably indirectly stimulate 5-HT1 receptors) was attempted in separate experiments with the 5-HT1 and 5-HT2 antagonist methysergide and the 5-HT neurotoxin 5,7-dihydroxytryptamine. Direct 5-HT1A agonists 8-hydroxy-2-(di-n-propylamino)tetralin and 5-methoxy-N,N-dimethyltryptamine and the 5-HT precursor 5-hydroxytryptophan all increased the reinforcement rate. The 5-HT1B and 5-HT1C agonists m-chlorophenylpiperazine and 1-(m-trifluoromethylphenyl)piperazine did not increase the reinforcement rate. The 5-HT2 agonist and 5-HT3 antagonist quipazine also did not increase the reinforcement rate. The monoamine oxidase inhibitor clorgyline and the 5-HT uptake inhibitor fluoxetine increased the reinforcement rate and decreased the response rate as seen with other antidepressant drugs on the DRL 72-s schedule. Methysergide antagonized the reinforcement rate increasing effects of both clorgyline and fluoxetine. Depletion of brain 5-HT with i.v.t. 5,7-dihydroxytryptamine blocked the antidepressant-like effects of clorgyline. These results suggest that central 5-HT1A receptors are involved in mediating the antidepressant-like effects of some drugs on DRL 72-s behavior. These results provide evidence that stimulation of 5-HT1A receptors and antagonism of 5-HT2 receptors lead to an antidepressant-like effect on the DRL 72-s schedule and implies that these two receptors may be important in mediating clinical drug effects in depression.
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PMID:Evidence for involvement of 5-hydroxytryptamine1 receptors in antidepressant-like drug effects on differential-reinforcement-of-low-rate 72-second behavior. 274 11

The effects of different synaptic antagonists on paired-pulse plasticity of medial perforant path responses were studied in rat hippocampal slices. Baclofen reduces the response to activation of the perforant path, but does not have the same net effect on the first and second responses to paired stimulation: baclofen lessens the percent paired-pulse depression of medial perforant path responses. Furthermore, at doses that reduced the control medial perforant path response by half, paired-pulse plasticity changed from paired-pulse depression to paired-pulse potentiation. A similar effect on medial perforant path paired-pulse plasticity is produced by decreasing extracellular calcium concentration. Kynurenic acid reduces the first and second responses to paired stimulation proportionately the same, and, therefore, has no effect on the percent paired-pulse depression. These results suggest that baclofen acts presynaptically to reduce the synaptic response, whereas kynurenate acts postsynaptically. Adenosine was also found to be a potent antagonist of medial perforant path responses, with effects on paired-pulse plasticity similar to baclofen: a new synaptic antagonist, N-p-chlorobenzoyl-piperazine-2,3-dicarboxylate, was found to have effects like kynurenate, suggesting that it is also a postsynaptic receptor blocker.
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PMID:Effects of synaptic antagonists on perforant path paired-pulse plasticity: differentiation of pre- and postsynaptic antagonism. 298 85

Buspirone (Buspar) is a azaspirodecanedione anxiolytic agent. Its mechanism of action is extremely complex, but current investigations indicate that its main neuropharmacologic effects are mediated by the 5-HT1A receptors. Other neuroreceptor systems could be involved, as buspirone displays some affinity for DA2 autoreceptors and 5-HT2 receptors. It has been proposed that inhibition of synthesis and release of serotonin result through the combined interactions of neuroreceptors and secondary messenger systems. This action leads to inhibition of the firing rate of 5-HT-containing neurons in the dorsal raphe. From this novel profile, that differs from that of the benzodiazepines, buspirone lacks anticonvulsant and muscle-relaxant properties, and causes only minimal sedation. The drug is rapidly absorbed after oral administration, with a mean bioavailability of 3.9%. After a single oral dose, the mean elimination half-life is 2.1 hours. Buspirone is mainly bound to albumin and alpha 1-acid glycoprotein. It is metabolized to an active metabolite 1-(2-pyrimidinyl) piperazine (1-PP). The mean elimination half-life of 1-PP is 6.1 hours. Buspirone is indicated in the treatment of generalized anxiety disorders. Its efficacy is comparable to the benzodiazepines. Its use in depression and panic disorders requires further investigation. When combined with alcohol or given alone, psychomotor impairment was not detected. Abuse, dependence, and withdrawal symptoms have not been reported. The frequency of adverse effects is low, and the most common effects are headaches, dizziness, nervousness, and lightheadness. Buspirone should be added to drug formularies and could represent a significant addition in psychopharmacology.
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PMID:Buspirone: an update on a unique anxiolytic agent. 304 84

The effects of a novel piperazine derivative (INO 2628) on sinus node pacemaker activity and atrial contractile force were investigated in isolated, blood-perfused dog atrium. Injections of INO 2628 (0.03-100 mumol) into the sinus node artery of the isolated atrium induced a dose-dependent decrease in sinus rate and an increase in contractile force. The positive inotropic effects at more than 10 mumol were accompanied by a transient negative inotropism. Propranolol did not affect the positive inotropic response to INO 2628, but it significantly suppressed positive chronotropic and inotropic responses to norepinephrine. Atropine at a dose which completely blocked negative chronotropic and inotropic responses to carbachol, produced a slight but significant depression of INO 2628-induced negative chronotropic responses; inotropic responses were unaffected. These results suggest that INO 2628 induces noncholinergic negative chronotropic and nonadrenergic positive inotropic responses in isolated dog atria.
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PMID:Negative chronotropic and positive inotropic effects of a unique cardioactive agent, N,N'-dicyclopropyl methyl piperazine (bis) hydrochloride (INO 2628), in isolated, blood-perfused dog atria. 324 39

The anticonvulsant effect of a series of 6-alkoxy-N,N-disubstituted-2-pyridinamines is described. An investigation was carried out to optimize the activity/side-effect ratio in this series of compounds. The most desirable profile was seen with 1-[6-(2-methylpropoxy)-2-pyridinyl]piperazine, 6, and this compound was selected for a more complete pharmacological evaluation. Overall, 6 has a pharmacological profile that is very similar to that of diphenylhydantoin (phenytoin). While nearly equipotent to phenytoin, animal studies suggest a fairly short duration of action. In addition, 6 exhibited some troublesome side effects including central nervous system depression and hypothermia.
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PMID:6-Alkoxy-N,N-disubstituted-2-pyridinamines as anticonvulsant agents. 359 26

Between September 1982 and January 1984, verminous colitis was diagnosed post mortem in eight red-footed tortoises (Geochelone carbonaria) and three leopard tortoises (Geochelone pardalis) from the reptile collection of the National Zoological Park. This represented 69% of 16 tortoise necropsy accessions for that period. Etiology was determined to be a viviparous pinworm-like nematode of the genus Proatractis (Family Atractidae). Clinical signs were either nonspecific, consisting of anorexia, lethargy, and depression, or were absent. Limited trials with piperazine citrate and fenbendazole appeared to be ineffectual against the parasite and supportive therapy was unsuccessful. Post mortem examination revealed roughening and thickening of the mucosa of the cecum and colon, and in severe cases myriads of tiny (0.5-1.0 cm) nematodes were evident on the mucosal surface. In six tortoises, worms were found also in the small intestine. Histopathologic features in severe cases included mucosal necrosis with parasites and mixed inflammatory cells extending into the tunica muscularis. Focal to diffuse lymphoplasmacytic infiltrates were present consistently in the submucosa of the cecum and colon, and similar but milder lesions occasionally occurred in the small intestine.
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PMID:Mortality of captive tortoises due to viviparous nematodes of the genus Proatractis (Family Atractidae). 382 Apr 11

1. The action of piperazine on mammalian smooth, cardiac and skeletal muscles has been studied.2. Piperazine increased tone and produced a dose dependent contraction of isolated smooth muscle, which was antagonized by atropine.3. With cardiac muscle, piperazine depressed both the rate and force of contraction and was antagonized by atropine. At higher concentrations, a non-specific depression of cardiac muscle was found. The intravenous injection of piperazine produced a transient decrease in both heart rate and blood pressure and this was followed by an increase.4. In about half of the mammalian skeletal muscle preparations, piperazine potentiated the twitch of the muscle evoked by electrical stimulation.5. On the frog neuromuscular preparation, piperazine produced potentiation of the twitch but this was followed first by blockade of the effects of nerve stimulation and then by depression of the effects of direct muscle stimulation.
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PMID:Some pharmacological properties of piperazine. 466 88

Fifty-five depressed menopausal patients took part in a randomized double-blind cross-over trial using ;Harmogen' (piperazine oestrone sulphate) and placebo. The Beck depression inventory, hot flush counts, and patients' subjective assessment of well-being were used to assess clinical status. Hormonal, biochemical and coagulation profiles were carried out. Hot flushes improved significantly on oestrogen compared with placebo. Depression scores and well-being showed significant and equal improvement on oestrogen and placebo. Significant improvement in flushes in patients on placebo was observed in the first half of the trial but did not occur in the second half, in patients who had previously taken oestrogen. No significant changes occurred in biochemistry. Coagulation tests showed acceleration of the prothrombin time in patients taking ;Harmogen' compared with those on placebo. Piperazine oestrone sulphate is a relatively weak but safe oestrogen preparation, effective in treatment of vasomotor symptoms but no more effective than placebo in the treatment of depression.
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PMID:Is oestrogen therapy effective in the treatment of menopausal depression? 626 83

A double-blind trial of piperazine oestrone sulphate was performed over a period of 14 months on 55 menopausal women complaining of depressiona and hot flushes. Depression was not affected but the hot flushes were significantly lessened by the oestrogen treatment. After three months of piperazine oestrone sulphate there were no significant accelerations of prothrombin time or increases in factors VII or X but, after six months, there was an acceleration in the prothrombin time. After 14 months those who received piperazine oestrone sulphate for the first six months showed a significant increase in alpha 1-antitrypsin and factor VIIR:AG. Oestrone piperazine sulphate appears to produce less marked changes in coagulation than oestrogen-containing oral contraceptives or conjugated equine oestrogens.
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PMID:A double-blind cross-over study of piperazine oestrone sulphate and placebo with coagulation studies. 700 Jan 69

Aspartame (APM) or L-aspartyl-L-phenylalanine, and a 3 : 1 combination of APM with its decomposition product, 5-benzyl-3,6-dioxo-2-piperazine acetic acid (DKP), were incorporated at levels of up to 4 g/kg in the diet of male and female Wistar rats from 6 weeks to 104 weeks of age. There was a dose-dependent depression of body weight gain at 2 and 4 g/kg AMP and at 4 g/kg APM + DKP in males, and at all dose levels in females, correlated with decreased food consumption and attributed to liberation of amino acids from hydrolysis of APM. Increases in urinary specific gravity and pH, with increase of relative kidney weight, were attributed to the urinary excretion DKP and acidic metabolites of APM. A dose-related increase in urinary calcium probably reflected increased calcium absorption, as from high protein diets. A slight decrease in serum cholesterol and an increase in relative spleen weight appeared to be without adverse effect. It is concluded that the treatments were without toxic effect.
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PMID:Toxicity of aspartame and its diketopiperazine for Wistar rats by dietary administration for 104 weeks. 728 Dec 5


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