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)

The arrival of clozapine has been one of the most significant developments in antipsychotic drug treatment since the advent of chlorpromazine ushered in the psychopharmacologic era. However, its utilization has been significantly limited and complicated by its potential to cause adverse effects and agranulocytosis in particular. It must be emphasized that clozapine has a side effect profile that is in many ways distinct from standard typical antipsychotic drugs. Side effects with clozapine are common and range from the benign to the potentially lethal. The most common side effects include sedation, dizziness, and sialorrhea during sleep; the most serious are agranulocytosis, seizures and respiratory depression. Although side effects from clozapine are not necessarily preventable, they are for the most part manageable. Even with the most serious adverse effects, proper knowledge of the medication's actions, clinical vigilance, and prompt intervention can prevent the occurrence of significant morbidity and mortality as a consequence of clozapine treatment.
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PMID:Clinical profile of clozapine: adverse reactions and agranulocytosis. 143 5

Examination of the neurobiology of psychiatric illness in general, and of affective disorders in particular, reveals a variety of associated biochemical abnormalities. These have generally been assumed to be part of the pathological process or secondary to it, and thus deserving of therapeutic efforts aimed at reversal. However, recent clinical and preclinical data suggest that some alterations occurring in the affective disorders may be compensatory and adaptive; that is, part of an endogenous therapeutic mechanism rather than part of the evolving disease process. For example, the symptom of sleep loss in depression seems to fall under this rubric inasmuch as sleep deprivation induces mood improvement in depressed patients. Preclinical data are presented that another primary pathological process--the occurrence of kindled seizures--can evoke endogenous compensatory processes that are either anticonvulsant in their own right, or enable the anticonvulsant effects of a drug such as carbamazepine. It may be that some biochemical abnormalities occurring in affective illness are similarly adaptive. As one example, increased thyrotropin-releasing hormone (TRH) has been reported in the cerebrospinal fluid (CSF) of depressed patients. This elevation of TRH and the resulting neuroendocrine profile may be part of an endogenous counter-regulatory process aimed at mood improvement. Again, preclinical seizure models are supportive in that TRH not only is induced following repeated seizures, but also exerts anticonvulsant effects on these same seizures. In an analogous fashion, TRH elevations in depressed patients may also exert ameliorating effects on depressive symptomatology. This formulation presents directly testable hypotheses that could importantly impact on our understanding of the pathophysiology of affective disorders, and suggests novel therapeutic strategies through the enhancement of endogenous compensatory mechanisms.
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PMID:Ziskind-Somerfeld Research Award 1992. Endogenous biochemical abnormalities in affective illness: therapeutic versus pathogenic. 144 65

The involvement of the dopaminergic (DA) systems in the control of limbic kindled seizures is ill defined. The effects of kindling on DA activity may have been overlooked in the past, because of its subtle unilateral occurrence and/or the variance of the endogenous imbalance of DA activity in normal animals. In the present study rats were screened for their endogenous DA imbalance using amphetamine-induced rotational behaviour. Electrical or sham kindling was applied in the hemisphere with the higher endogenous DA activity. Sections of the bilateral prefrontal cortex and dorsal and ventral striatum were dissected either 2 hours or 21 days after the final seizure and the electrically stimulated release of [3H]DA and [14C]acetylcholine (ACh) determined. Release was also measured in the presence of quinpirole or sulpiride to assess the activity of pre- and postsynaptic DA D2-receptors. Long-term effects of kindling consisted of facilitation of ACh release in the ventral striatum contralateral to the kindled amygdala and bilateral depression of DA release in the prefrontal cortex. Kindling therefore produced area specific changes in neurotransmitter systems giving rise to increased pro-convulsive cholinergic activity in the ventral striatum and decreased anti-convulsive dopaminergic activity in the prefrontal cortex.
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PMID:Effect of amygdaloid kindling on [3H]dopamine and [14C]acetylcholine release from rat prefrontal cortex and striatal slices. 145 Sep 3

To characterize the convulsions induced by an aqueous extract of Palicourea marcgravii (Pm), male Wistar rats were injected sc with 3.75 g/kg of the extract, and electroencephalogram and behavior were observed for periods up to 180 min after the Pm injections. Sleep spindles and generalized convulsive seizures were observed following Pm administration. Spiking activity was detected in both cortical and hippocampus recordings. They lasted approximately 2 min and were followed by a period of postical depression and/or death. These results agreed with previous behavioral experiments which suggested the toxic effect of Pm aqueous extract was mainly at the central nervous system level.
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PMID:The relationships between neuronal activity and behavioral seizures induced by Palicourea marcgravii in rats. 145 2

We tested the hypothesis that brain somatostatin levels modify two motor behaviors evoked by ICV infusions of nicotine. Unrestrained, awake rats were given fixed-concentration infusions of nicotine until the prostration/immobility (PI) syndrome and convulsions were produced. Infusion duration ranged from 0.9 to 1.2 min for the PI syndrome and 2.5 to 4.9 min for the convulsions. Octreotide, a stable somatostatin analog (4.5 micrograms, ICV), significantly raised the threshold for nicotine convulsions 1.0 and 5.5 h after pretreatment but not at 24 or 48 h. Cysteamine, a somatostatin releaser and depletor (0.35-0.75 mg/rat, ICV), also caused a dose-dependent increase in seizure threshold. Similarities in the response to octreotide and cysteamine suggest that depression of nicotine convulsions by cysteamine may be mediated by release of endogenous somatostatin. Neither octreotide nor cysteamine altered the threshold for the PI syndrome. These results support the view that one motor behavior evoked by nicotine is subject to control by somatostatin whereas another is not.
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PMID:Differential effects of octreotide on motor responses to nicotine in rats. 147

The demonstration that the immediate-early gene c-fos is rapidly and transiently expressed in brain following a variety of manipulations has led to intense study of these genes to determine what physiological role they play. The very wide range of stimuli which lead to induction of immediate-early genes (IEGs) in the brain has raised concerns for the specificity of their actions and the suggestion that they might merely be involved in housekeeping functions. On the other hand, there is evidence that these genes may play a role in the transmission of information from cell surface receptors to the genetic material in many instances of neuronal plasticity, including development of seizure susceptibility (kindling), long-term potentiation, drug-induced changes, the phase shift in circadian rhythms, and spreading neuronal depression. In addition to being a putative third (or fourth) messenger involved in transduction of signals to the genetic material, activation of IEGs has proven to be a useful tool for the study of transsynaptic activation of certain neuronal pathways in the brain. Thus, studies on the induction of IEGs are proving to be especially useful in understanding some important functions and properties of the mammalian brain.
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PMID:Immediate-early genes, neuronal plasticity, and memory. 148 50

The selective serotonin reuptake inhibitors (SSRIs) are a tribute to the ingenuity of pharmacologists and designers of molecules. Not only do these drugs have remarkable selectivity for the reuptake of serotonin compared with other monoamines, but also they have a commendable lack of affinity for receptors including the serotonin receptor. In contrast, the classical tricyclic antidepressants (TCAs) are less specific in their pharmacological action. In addition to inhibiting the reuptake of serotonin, TCAs inhibit the uptake of noradrenaline, dopamine and tyramine, and antagonize cholinergic (muscarinic), adrenergic and histaminergic receptors. Moreover, TCAs have quinidine-like anti-arrhythmic activity and lower the seizure threshold. Clinical investigations have shown that the SSRIs have equivalent therapeutic efficacy compared with the TCAs in the treatment of depression. However, the pharmacological specificity of the SSRIs is a clinical advantage since they lack the propensity to cause dry mouth, blurred vision, urinary hesitancy, constipation, hypotension and arrhythmia. Furthermore, the SSRIs are relatively safe in overdosage. The similarities between the SSRIs are more obvious than their differences: all are highly potent and selective inhibitors of serotonin reuptake with efficacy in the treatment of depression. Nevertheless, each has a distinctive pharmacological profile. In this review the characteristics desired in an "ideal" antidepressant are examined, and the ways in which the TCAs and SSRIs fit this ideal are compared.
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PMID:Clinical implications of the pharmacology of serotonin reuptake inhibitors. 148 74

In a series of studies, we have explored the nature of memory problems experienced by people with epilepsy. By means of a questionnaire, the first study surveyed everyday memory failures experienced by 742 people with epilepsy. Findings revealed a high level of failures that were associated with later age of onset of seizures and raised levels of anxiety and depression. A second smaller prospective study confirmed these findings and suggested that patients with epilepsy had underestimated the frequency of memory complaints when assessed retrospectively. The third study investigated the relationship between self-reported memory failures and neuropsychological test performance. A measure of verbal recall was the best predictor of reported memory failures. Again, older age of onset and mood were found to be pertinent variables in relation to memory complaints.
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PMID:Everyday memory failures in people with epilepsy. 148 31

A 4-year-old German Shepherd Dog was evaluated because of chronic hind limb lameness and recurrent seizures. Diagnostic evaluation of the dog confirmed rheumatoid arthritis and idiopathic epilepsy. The rheumatoid arthritis was treated with prednisone and piroxicam. The seizures were treated with phenobarbital plus clonazepam. The seizures were refractory and potassium bromide was substituted for clonazepam. The dog was reevaluated 4 months after initiation of potassium bromide treatment because of recurrence of arthritis signs. During hospitalization, the dog had neurologic signs, which progressed from depression to recumbency and stupor. Anisocoria, muscle pain, and hyporeflexia were noticed. Bromide toxicosis was diagnosed on the basis of toxic serum bromide concentration (2.7 mg/ml; therapeutic range, 1.0 to 2.0 mg/ml). Following cessation of potassium bromide treatment, the neurologic signs resolved. The seizures recurred 6 weeks after potassium bromide was discontinued. Bromide treatment was reinitiated at half the initial dosage. After 6 weeks, the serum bromide concentration was 1.9 mg/ml, and no seizures had been reported by the dog's owners. Therapeutic serum bromide concentrations in dogs has been reported to be 0.5 to 2.3 mg/ml. The serum bromide concentration at which toxic signs are expected is variable in human beings because individuals differ in their tolerance of the drug. Clinical trials are necessary to determine the toxic serum bromide concentrations in dogs. This case of bromism in a dog suggests that the dosage of potassium bromide should be based on serial measurement of serum bromide concentrations.
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PMID:Bromide toxicosis (bromism) in a dog treated with potassium bromide for refractory seizures. 148 95

Fully amygdala kindled rats were exposed to two different inter-male agonistic experiences in order to study the interaction between epilepsy and acute social stress. Victory experience did not influence the severity of seizure behaviour, whereas a single acute defeat modified both ictal and postictal seizure manifestations. Defeat resulted in less severe and shorter lasting motor seizures, and the accompanied postictal inhibition or behavioural depression was of shorter duration in comparison with pre-stress values. The ability of acute defeat to trigger anticonvulsant activity as implied by the weakened convulsive response is discussed.
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PMID:Effect of different agonistic experiences on behavioural seizures in fully amygdala kindled rats. 150 89


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