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)

Because of the limitations in efficacy and safety of the older tricyclic antidepressants (TCA) and monoamine oxidase inhibitors (MAOI) a number of new approaches have been made in recent years to the treatment of depression to obtain more effective, more rapidly acting, better tolerated and safer drugs. One tactic has been to develop compounds with greater neuropharmacological selectivity in inhibiting the neuronal reuptake of 5-HT. Most of these are as effective as TCA but with fewer side-effects and greater safety. Another development has been 'reversible' MAOI which reduce the risk of interaction with tyramine-containing foods. For resistant depression the addition of lithium (and/or tryptophan) may be effective, possibly through promoting 5-HT neurotransmission. Continuous treatment with a selective 5-HT reuptake inhibitor can reduce the relapse rate in patients with recurrent depression. Unfortunately, these new approaches, despite their advantages in terms of side-effects and safety, have thus far not proved to be more effective or faster acting than the standard TCA. That remains a challenge for the future.
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PMID:New aspects in the treatment of depression. 143 Oct 20

Dopamine (DA) causes a dose-dependent increase in the frequency of motor neuron bursts [virtual ventilation (fR)] produced by deafferented crab ventilatory pattern generators (CPGv). Domperidone, a D2-specific DA antagonist, by itself reversibly depresses fR and also blocks the stimulatory effects of DA. Serotonin (5HT) has no direct effects on this CPGv. Nicotine also causes dramatic dose-dependent increases in the frequency of motor bursts from the CPGv. The action is triphasic, beginning with an initial reversal of burst pattern typical of reversed-mode ventilation, followed by a 2- to 3-min period of depression and then a long period of elevated burst rate. Acetylcholine chloride (ACh) alone is ineffective, but in the presence of eserine is moderately stimulatory. The inhibitory effects of nicotine are only partially blocked by curare. The excitatory action of nicotine is blocked by prior perfusion of domperidone, but not by SKF-83566.HCl, a D1-specific DA antagonist. SKF-83566 had no effects on the ongoing pattern of firing. These observations support the hypothesis that dopaminergic pathways are involved in the maintenance of the CPGv rhythm and that the acceleratory effects of nicotine may involve release of DA either directly or via stimulation of atypical ACh receptors at intraganglionic sites.
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PMID:Dopamine and nicotine, but not serotonin, modulate the crustacean ventilatory pattern generator. 143 39

In order to test the effects of various biological treatments on serotonergic function in depression, twenty-one patients with a diagnosis of major depression underwent neuroendocrine challenge tests before and after treatment with either ECT, fluoxetine or amitriptyline. The serotonin (5-HT) releasing agent d-fenfluramine was used as a challenge drug and cortisol (CORT) and prolactin (PRL) plasma levels were monitored over a 5-h period. Overall PRL responses were significantly enhanced following pharmacotherapy irrespective of therapeutic outcome. Effective treatment in each case lowered baseline CORT levels but CORT response to d-fenfluramine remained blunted. Hypercortisolaemia may be involved in the impaired pretreatment PRL response as a strong inverse relationship was established, for the combined studies, between basal CORT plasma concentrations and PRL responses.
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PMID:D-fenfluramine-induced prolactin and cortisol release in major depression: response to treatment. 146 Jan 63

1. Three ipsilateral (MSR, PSR, IPSI SLOW) and two contralateral segmental reflexes (CON FAST, CON SLOW) were recorded from L4 or L5 ventral roots of the neonate rat spinal cord in vitro. MSR, PSR and CON FAST were evoked from lower threshold afferents; more intense stimulation evoked IPSI SLOW and CON SLOW. 2. Kainate/AMPA receptors were involved in mediation of MSR, PSR, CON FAST, IPSI SLOW and CON SLOW and NMDA receptors in mediation of CON FAST, IPSI SLOW and CON SLOW. 3. All five reflexes were depressed by 5-HT (IC50 1.2-7.9 microM; order of sensitivity, CON SLOW > CON FAST = IPSI SLOW > MSR = PSR); and by 5-CT (IC50 1.9-8.8 nM; order of sensitivity, MSR > IPSI SLOW = CON FAST = CON SLOW > PSR). alpha-Me-5-HT also depressed all five reflexes. 4. Dipropyl-5-CT selectively depressed MSR and CON SLOW (IC50 90-170 nM) but was less potent than 5-CT. 8-OH-DPAT selectively depressed MSR (IC50 1.1 microM), IPSI SLOW and CON SLOW (IC50 5.7-7.6 microM), while methylsergide depressed only MSR (IC50 26 nM). 5. Phenyl biguanide and m-chlorophenyl biguanide (5-HT3 receptor agonists) had no significant effects on any reflex. 6. It is concluded that a 5-HT1-like receptor mediates depression of the MSR. A different receptor or a mixed population of receptors, but not 5-HT3 receptors, mediate inhibition of PSR, CON FAST, IPSI SLOW and CON SLOW.
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PMID:FAST and SLOW ipsilateral and contralateral spinal reflexes in the neonate rat are modulated by 5-HT. 148 13

The past decade has seen important progress in understanding the localization, pharmacology, and function of serotonin (5-HT) receptor subtypes. At least seven subclasses have been shown to exist, and evidence is emerging to suggest further subclassification. Serotonin is involved in numerous physiological processes (e.g. feeding, sleep, pain, sexual behavior, temperature regulation) and pathophysiological ones. Serotonin reuptake blockers have been found effective in the alleviation of depression and attacks of panic, and are at varying stages of clinical evaluation in the treatment of obsessive compulsive disorder, chronic pain, and bulimia nervosa. Selective potent serotonin receptor agonists and antagonists show promise in the treatment of migraine, nausea and vomiting, schizophrenia, anxiety, hypertension, and Raynaud's disease.
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PMID:[New therapeutic possibilities with drugs affecting serotonin receptors]. 150 27

Obsessive-compulsive disorder is a well-defined clinical syndrome that has been difficult to treat with standard psychotherapies and medications. Data accumulated over the last decade have demonstrated that the disorder is relatively common and frequently coexists with phobia, depression, and alcohol abuse. The authors review current studies of the spectrum of obsessive-compulsive disorder and related disorders that respond to the new serotonergic antidepressants and behavioral therapy. Differential diagnosis, epidemiology and comorbidity, etiology, evaluation, and psychologic and pharmacologic treatments are discussed. Most patients with obsessive-compulsive disorder require long-term treatment with drugs, but behavioral therapy has also been used successfully. Serotonin reuptake inhibitors used in the treatment of depression have been found effective; clomipramine has produced the best results in large-scale tests. The fact that serotonin reuptake inhibitors are effective as both antidepressants and antiobsessional agents suggests common biological factors in disorders that respond to these drugs.
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PMID:Obsessive-compulsive disorder. 151 99

Ablation of olfactory bulbs in rats reduced male sexual behavior, and altered the distribution of wheel-running activity between the light and dark phases of a 12:12 LD photoperiod. These effects were partially reversed by the tricyclic antidepressant amitriptyline. Olfactory bulbectomy also altered serotonin metabolism (5-HIAA/5-HT ratio) in the frontal cortex, nucleus accumbens, hippocampus and corpus striatum. These observations support the hypothesis that olfactory bulbectomy in rodents serves as a model of agitated hyposerotonergic depression.
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PMID:Olfactory bulbectomy as a model for agitated hyposerotonergic depression. 152 54

Specific sleep disturbances such as reduced slow-wave sleep (SWS) and decreased serotonergic (5-HT) activity have been observed in depressive disorders. Ritanserin, a specific 5-HT2 receptor antagonist, has been shown to increase SWS in healthy subjects. This study explored the effects of a single dose or ritanserin (5 mg) on sleep electroencephalography in 18 major depressed patients and in 10 control subjects. Ritanserin affected SWS differently in the two groups. Although stage 3 increased significantly in the groups, in contrast to controls, there was no significant effect of ritanserin on stage 4 in depressed patients. In the depressed group, irritability and DSM-III-R melancholic type predicted 40% or the variance of stage 4 increment after ritanserin, as assessed by stepwise multiple regression. These results are in agreement with a potential 5-HT disturbance, particularly at the 5-HT2 receptor level, in some clinical forms of depression.
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PMID:5-HT2 receptor antagonism and slow-wave sleep in major depression. 152 36

The 5-hydroxytryptamine1A (5-HT1A) receptor subtype seems to be of importance in the pathogenesis of depression and in the mode of action of antidepressants. In this study, behavioural experiments were performed in rats after oral administration of desipramine for 18-20 days, followed by an acute injection of the selective 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), either systemically or intrathecally. Chronic administration of desipramine prolonged the behavioural 5-HT syndrome in the animals injected systemically with 8-OH-DPAT. Treatment with desipramine was also found to potentiate and prolong the antinociceptive effect of an acute injection, systemically or intrathecally, of 8-OH-DPAT in the increasing temperature hot plate test. After systemic administration of 8-OH-DPAT, the colonic temperature was lowered similarly in the desipramine-treated group and in controls, whereas an intrathecal injection of 8-OH-DPAT resulted in a fall in the colonic temperature in the desipramine-treated group only. In vitro receptor binding studies, using [3H]8-OH-DPAT as the ligand, showed a statistically significant reduction of Kd and Bmax in the frontal cortex and of Kd in the spinal cord, after treatment with desipramine. No changes of Kd and Bmax were found in the hippocampus after this treatment. Thus, desipramine, administered chronically, resulted in a functional up-regulation of the 5-HT1A-receptors, both spinally and supraspinally, whereas in the in vitro receptor binding, a slight down-regulation or no change was found. It seems therefore that the results of in vitro receptor binding studies do not necessarily reflect the functional state of the neuronal system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Desipramine, administered chronically, influences 5-hydroxytryptamine1A-receptors, as measured by behavioral tests and receptor binding in rats. 153 64

The major complications of therapy in PD are motor, autonomic and psychiatric. Motor complications may be associated with altered striatal bioavailability of levodopa, and may in part respond to changes in timing of drug administration, redistribution of dietary protein and the use of controlled-release preparations. Since long-term complications seem to be associated with higher cumulative doses of levodopa, the early use of adjunctive agents such as deprenyl and/or dopamine agonists is encouraged. Autonomic effects include impaired bladder and bowel function, impotence and postural hypotension. If conservative measures are ineffective, pharmacotherapy with domperidone, fludrocortisone, indomethacin or adrenergic agents may be required. Depression in PD is associated with decreased levels of noradrenaline and 5-HT and responds to tricyclic antidepressants. Drug-induced psychosis reflects stimulation of mesolimbic-cortical dopamine receptors. Alternatives include reduction of medication, the use of atypical neuroleptics (which may act at novel subtypes of the dopamine receptor) and electroconvulsive therapy.
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PMID:Prevention and management of late stage complications in Parkinson's disease. 157 55


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