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)

Chronically implanted rats were injected either with somatostatin (SST) lumbar intrathecally (i.t.) (100 micrograms, n = 5), into the fourth ventricle (3 micrograms, n = 5; 10 micrograms, n = 6; 30 micrograms, n = 5) or into the lateral ventricle (10 micrograms, n = 6; 30 micrograms, n = 6), or received an injection of the substance P (SP) analogue, [D-Pro2, D-Trp7,9]SP into the fourth ventricle (0.3 micrograms, n = 2; 1 micrograms, n = 4; 3 micrograms, n = 4; 10 micrograms, n = 1) or lateral ventricle (3 micrograms, n = 3). A dose-dependent EEG depressant effect was observed following fourth and lateral ventricular injections of SST and of the SP analogue. Acute death due to respiratory depression was observed following i.t. and fourth ventricular injection of SST, and fourth ventricular injection of the SP analogue. Prominent motor behavior (barrel rotation, circling, cranial stereotypies) was observed, without signs of EEG seizure activity, following intraventricular injection of both drugs. Present findings indicate neurotoxic effects of SST and SP analogue at the cerebral level.
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PMID:Electroencephalographic and behavioral assessment of intracerebroventricular somatostatin and a substance P analogue. 247 57

The novel antidepressant moclobemide is a reversible inhibitor of monoamine oxidase (MAO), preferentially of type A. Moclomide was active in three animal models considered predictive for antidepressant activity: 1) it prevented dose-dependently akinesia and blepharospasm induced in mice and rats by Ro 4-1284, a short-acting amine releasing agent. Prevention of akinesia by moclobemide also depended upon the dose of Ro 4-1284. For comparison also, effects of cimoxatone, harmaline, tranylcypromine and clorgyline are presented: 2) in cats, it selectively and dose-dependently suppressed rapid eye movement sleep without disturbing the sleep-wakefulness cycle; and 3) in the behavioral despair test in mice, it decreased the immobility score to a similar degree as amitriptyline or imipramine. In addition, moclobemide potentiated 5-hydroxytryptophan-induced stereotypies in rats with a potency similar to cimoxatone and with a duration of action of less than 24 hr. Moclobemide had almost no effect on the spontaneous behavior in mice, rats, cats and monkeys. Only in higher doses, marginal sedation and slight impairment in motor performance were seen. Moclobemide did not prevent pilcarpine-induced salivation in mice, demonstrating the absence of anticholinergic activity. Blood pressure and heart rate of freely moving, spontaneously hypertensive rats were only slightly decreased for less than 3 hr. Moclobemide moderately potentiated the pressor effect of p.o. tyramine in rats. In conclusion, the reversible MAO inhibitor moclobemide is active in animal models sensitive to all major drugs used in the treatment of depression. In contrast to imipramine-like antidepressants, it lacks anticholinergic activity and it differs from classic MAO inhibitors by potentiating only weakly the pressor effect of p.o. tyramine.
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PMID:Pharmacological profile of moclobemide, a short-acting and reversible inhibitor of monoamine oxidase type A. 291 84

From the data discussed in this review it appears that GABA receptor agonists exhibit a variety of actions in the central nervous system, some of which are therapeutically useful (Table V). GABA receptor agonists, by changing the firing rate of the corresponding neurons accelerate noradrenaline turnover without changes in postsynaptic receptor density and diminish serotonin liberation with an up-regulation of 5HT2 receptors. These effects differ from those of tricyclic antidepressants which primarily block monoamine re-uptake and cause down-regulation of beta-adrenergic and 5HT2 receptors. The GABA receptor agonist progabide has been shown to exert an antidepressant action which is indistinguishable from that of imipramine in patients with major affective disorders. The fact that: (a) GABA receptor agonists and tricyclic antidepressants affect noradrenergic and serotonergic transmission differently; and (b) tricyclic antidepressants alter GABA-related parameters challenges the classical monoamine hypothesis of depression and suggests that GABA-mediated mechanisms play a role in mood disorders. Decreases in cellular excitability produced by GABAergic stimulation leads to control of seizures in practically all animal models of epilepsy. GABA receptor agonists have a wide spectrum as they antagonize not only seizures which are dependent on decreased GABA synaptic activity but also convulsant states which are apparently independent of alterations in GABA-mediated events. These results in animals are confirmed in a wide range of human epileptic syndromes. GABA receptor agonists decrease dopamine turnover in the basal ganglia and antagonize neuroleptic-induced increase in dopamine release. On repeated treatment, progabide prevents or reverses the neuroleptic-induced up-regulation of dopamine receptors in the rat striatum and antagonizes the concomitant supersensitivity to dopaminomimetics. Behaviorally, GABA receptor agonists diminish the stereotypies induced by apomorphine or L-DOPA suggesting that GABAergic stimulation results also in an antidopaminergic action which is exerted beyond the dopamine synapse. These effects of GABA receptor agonists may represent the basis of the antidyskinetic action of these compounds which, however, remains to be fully confirmed. GABA receptor agonists reduce striatal acetylcholine turnover, an effect which occurs at doses much lower than those which affect dopamine neurons. Since hyperactivity of cholinergic neurons plays a determinant role in the pathogenesis of some parkinsonian symptoms, it is conceivable that GABAergic stimulation is effective in ameliorating Parkinson's disease.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:GABA receptor agonists: pharmacological spectrum and therapeutic actions. 298 90

The association of Pick's Disease (PD) and Amyotrophic Lateral Sclerosis (ALS) as a familial syndrome is reported for the first time. Four members in two generations of the investigated family suffered from this syndrome, allowing the hypothesis of a dominant mode of inheritance. PD is primary, with onset at 58 to 67 years: loss of interests, depression, aggressivity, perseveration , stereotypies, reduction of speech until total mutism; a few months later appear ALS signs: fasciculations and/or pyramidal symptoms. The total evolution is 3 to 5 years. The brain showed a fronto-temporal atrophy spreading to the precentral gyrus with cortical and white matter gliosis, neuronal loss, atrophic neurons and some ballooned cells, but without senile plaques (SP), neurofibrillary tangles (NFT) or cortical spongiosis; the spinal cord and the medulla oblongata showed typical ALS lesions; mild lesions in the basal nuclei, particularly in the substantia nigra and the pallidum. The differential diagnosis is discussed with: Alzheimer's Disease + ALS (SP + NFT); the Guam syndrome (NFT); Creutzfeldt-Jakob's Disease (cortical microspongiosis); ALS + dementia (primary ALS); Mitsuyama's syndrome (primary dementia and secondary ALS, but with cortical spongiosis and without familial incidence).
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PMID:[A familial syndrome: a combination of Pick's disease and amyotrophic lateral sclerosis]. 332 1

A 68 year-old man with a history of right thalamic hemorrhage demonstrated radiologically in the pulvinar and posterior portion of the dorsomedian nucleus developed a clinical picture of severe physical sequelae associated with major affective, behavioral and psychic disorders. Affective manifestations were a permanent anxiety-depression state contrasting with indifference to his surroundings. Behavioral changes included marked apathy, inertness and hypersomnia, together with occasional clastic agitated episodes and verbal and gestural stereotypies and soliloquies. Psychic sequelae were psychotic in nature: depersonalization crises, delusions of persecution, multisensorial hallucinations and absurd acts.
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PMID:[Thalamic dementia after a unilateral hemorrhagic lesion of the right pulvinar]. 382 7

Antagonism of ethanol-induced depression of locomotion was observed after intracisternal injection of thyrotropin releasing hormone (TRH) and bicuculline methiodide (BICM), as well as after microinjection of these drugs into the medial septum. The present investigation compared the behavioral and physiological consequence of administering TRH and BICM into the medial septum, inferior colliculus and substantia nigra to quantitate the similarities between these compounds. BICM produced a major increase in locomotor activity when injected into the medial septum and stereotypies when injected into the substantia nigra, suggesting that GABA-containing neurons have widespread influences on motor function. The wild running and seizure activity observed after BICM injection into the inferior colliculus was also consistent with this latter view. The marked increase in rectal temperature observed when BICM was injected into the medial septum may also implicate GABAergic mechanisms in temperature control at this brain site. TRH produced no such behavioral or physiological changes when administered into these three sites. Thus, this work strongly suggests that TRH does not exert a widespread action as a GABA antagonist because TRH did not produce the same changes induced by BICM. The actions of BICM and TRH to antagonize ethanol-induced depression when microinjected into the medial septum suggests that this brain area may be a critical site for the depressant action of ethanol.
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PMID:Comparison of the CNS effects induced by TRH and bicuculline after microinjection into medial septum, substantia nigra and inferior colliculus: absence of support for a GABA antagonist action for TRH. 643 50

1. The effects of the glycine/NMDA receptor partial agonists, D-cycloserine and (+)-HA-966 and the full agonist, D-serine, on focal seizure threshold and behaviour have been determined in amygdala-kindled rats, i.e. a model of focal (partial) epilepsy. The uncompetitive NMDA receptor antagonist, MK-801, was used for comparison. 2. The high efficacy glycine partial agonist, D-cycloserine, did not alter the threshold for induction of amygdaloid afterdischarges (ADT) at doses of 20-80 mg kg-1 i.p., but significant ADT increases were determined after application of higher doses (160 and 320 mg kg-1). The ADT increases after these high doses were long-lasting; significant elevations were still observed 2 days after drug injection. Determination of D-cycloserine in plasma and brain tissue showed that it was rapidly eliminated from plasma. Compared to peak levels in plasma, only relatively low concentrations of D-cycloserine were measured in brain tissue. 3. The low efficacy glycine partial agonist, (+)-HA-966, 10-40 mg kg-1 i.p., did not alter the ADT or seizure recordings (seizure severity, seizure duration, afterdischarge duration) at ADT currents. However, the drug dose-dependently increased the duration of postictal behavioural and electroencephalographic depression in kindled rats. At the higher dose tested, postictal immobilization was dramatically increased from 3 min to about 120 min. This might indicate that glutamatergic activity is decreased postictally, which is potentiated or prolonged by (+)-HA-966. 4. Like D-cycloserine, the glycine receptor full agonist, D-serine, injected bilaterally into the lateral ventricles at a dose of 5 mumol, significantly increased the ADT, while no effect was seen at a lower dose (2.5 mumol). 5. The anticonvulsant effects observed with D-cycloserine were completely antagonized by combined treatment with (+)-HA-966, indicating that the effects of D-cycloserine were mediated by the glycine/NMDA receptor complex. 6. MK-801, 0.1 mg kg-1, did not alter the focal seizure threshold or seizure recordings at ADT current, but induced marked phencyclidine(PCP)-like behavioural alterations, such as hyperlocomotion, stereotypies and motor impairment. No PCP-like behaviours were observed after D-cycloserine, D-serine or (+)-HA-966. High doses of (+)-HA-966 induced moderate motor impairment in kindled rats. 7. The long lasting increases in seizure threshold observed after the high efficacy glycine partial agonist,D-cycloserine but not the low efficacy partial agonist, (+)-HA-966, may suggest that the effects of D-cycloserine are mediated by adaptive changes in the NMDA receptor complex in response to glycine receptor stimulation.8. Pharmacological intervention at the strychnine-insensitive glycine receptor by high-efficacy partial agonists with systemic bioavailability may be an effective means of increasing seizure-threshold without concomitantly inducing PCP-like adverse effects.
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PMID:Anticonvulsant effects of the glycine/NMDA receptor ligands D-cycloserine and D-serine but not R-(+)-HA-966 in amygdala-kindled rats. 803 69

Recent brain imaging studies suggest that schizophrenia may be related to abnormally high amphetamine-induced dopamine release. It is known that repeated use of amphetamine may cause paranoid psychosis and persisting stereotypies. The biochemical background for these signs and symptoms has not been clarified. In this study, positron emission tomography and [11C]raclopride were used to determine central D2-dopamine receptor density (Bmax) and apparent affinity (K(D)app) in Cynomolgus monkeys before and after 14 days of treatment with d-amphetamine sulphate (2 mg/kg/day; s.c.). One day after withdrawal from amphetamine, K(D)app was increased, suggesting [11C]raclopride competition with elevated concentration of dopamine. At 7 and 14 days after withdrawal, there was a 19-26% decrease in Bmax but no change in K(D)app as compared to baseline. Although this study was performed on two monkeys only, there was thus no support for the view that chronic intermittent hyperactivity of the dopamine system may be related to an upregulation of striatal D2-dopamine receptors. Repeated administration of amphetamine may, rather, cause a long-lasting downregulation of the D2-receptor density, which may be a neurochemical correlate to the abnormal movements, anhedonia, anxiety, and depression seen in psychostimulant abusers.
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PMID:Changes in striatal D2-receptor density following chronic treatment with amphetamine as assessed with PET in nonhuman primates. 1002 13

Rat bilateral olfactory bulbectomy (OBX) serves as a useful model in the study of depression and the mechanisms of action of antidepressant treatments. Considering the evidence of NMDA receptors involvement in depression, the present study was undertaken in order to investigate the time-course effects of OBX on the NMDA receptor function. Following bilateral olfactory bulbectomy, rats display an increase in locomotor activity and changes in other types of behavior in a novel environment. Autoradiographic experiments using the noncompetitive NMDA antagonist [(125)I]-iodo-MK-801 as the labeling agent showed that this increase in behavioral activities corresponds to a decrease in [(125)I]-iodo-MK-801 binding in a number of brain regions. In most regions, this reduction reached significance by the third week following OBX. However, in some cortical areas-a nucleus of the thalamus (AV) and one of the amygdala (LA)-this reduction was already significant in the first or second week following OBX and lasted throughout the 4 weeks of the study. We also compared the behavioral modifications induced by a challenge injection of MK-801 (0.2 mg/kg i.p.) in OBX and sham-operated rats. This challenge is known to induce hyperlocomotion and a number of stereotypies in naive rats. These effects were drastically reduced in OBX as compared to sham-operated rats. These data are consistent with the above-mentioned decrease in cerebral binding of MK-801 to NMDA receptors.
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PMID:Effects of bilateral olfactory bulbectomy on N-methyl-D-aspartate receptor function: autoradiographic and behavioral studies in the rat. 1157 46

Antipsychotic drugs are used to treat a wide variety of child psychiatric disorders characterized by psychotic symptoms, aggression, excitement, tics, stereotypies and hyperactivity nonresponsive to other therapies. Unfortunately, typical antipsychotics have many adverse effects limiting their long-term use. Novel antipsychotics with combined dopaminergic and serotonergic action, such as risperidone, appear to offer better safety and efficacy profiles in controlled studies of adult patients, and therefore appeared as promising pharmacotherapeutic agents in child psychiatry. The purpose of this retrospective chart review was to obtain data on the potential effectiveness and tolerability of risperidone in children and adolescents presenting with a variety of chronic and severe psychiatric disorders who had been unresponsive to previous pharmacological treatments. Charts for 106 children and adolescents (males n = 81 or 76.4%; females n = 25 or 23.6%), presenting with attention deficit and/or hyperactivity disorder (n = 49 or 46.2%), conduct disorder (n = 13 or 12.3%), oppositional-defiant disorder (n = 5 or 4.7%), behavioural problems not otherwise specified (n = 2 or 1.9%), autism (n = 8 or 7.5%), Asperger's syndrome (n = 8 or 7.5%), pervasive developmental disorder (PDD) not otherwise specified (n = 4 or 3.8%), anxiety (n = 6 or 5.7%), depression (n = 2 or 1.9%), dysthymia (n = 2 or 1.9%), schizophrenia (n = 4 or 3.8%), adjustment disorder (n = 1 or 0.9%) and obsessive-compulsive disorder (n = 2 or 1.9%) were reviewed retrospectively to determine the tolerability and potential efficacy of risperidone treatment for a variety of psychiatric disorders. Six subjects also presented with mental retardation. The average length of illness prior to risperidone treatment was 5 years and the average age of risperidone treatment onset was 11 years. The mean daily dose of risperidone was 1.2 mg (range = 0.25 to 8.0 mg). Very few adverse effects were reported. The average length of risperidone treatment was 11 months with the majority (n = 75 or 76%) of patients maintained on risperidone following study termination. Seven cases (6.6%) were missing follow-up data. The majority (n = 78 or 74%) of patients were taking concurrent psychiatric medications, most commonly stimulants for the treatment of ADHD. Clinical global improvements for children and adolescents at the final study visit were marked (n = .37 or 34.9%), moderate (n = .40 or 37.7%), mild (n = 13 or 12.4%), none (n = 12 or 11.3%), or worse (n = 1 or 1%). Three cases (2.9%) were missing clinical improvement data. Results suggest that risperidone may be useful for managing behavioural disturbances and psychotic symptoms associated with a wide variety of childhood psychiatric disorders. For most patients in the study, a combination of risperidone and adjunctive pharmacotherapy was beneficial. Controlled and discontinuation studies of risperidone treatment in children and adolescents with behavioural and psychotic disorders are recommended.
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PMID:A retrospective chart review of risperidone use in treatment-resistant children and adolescents with psychiatric disorders. 1181 3


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