Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085631 (agitation)
 12,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sedative drugs are intended to cause various degrees of drowsiness. Animal experiments indicate that barbiturates induce these effects primarily by depression of the reticular activating system in the rostral brainstem. This in turn potentiates the thalamic recruiting system, thereby inducing 'barbiturate bursts' in the EEG. Anxiolytic drugs are intended to reduce anxiety or tension at doses which do not cause sedation or sleep. Propanediols may depress deactivating centers in the caudal brainstem, thereby releasing the activating centers in the rostral brainstem and depressing the thalamic recruiting response. These drugs may also act on the amygdala. Benzodiazepines have depressant effects on the amydala or hippocampus. These effects may release the reticular formation from inhibition. Enhanced activity of the activating and deactivating centers, to a different extent in different animals, would produce restlessness in some animals and sedation in others, accompanied by a mixture of fast and slow waves in the EEG. Sedative and anxiolytic agents also have central relaxant effects. The barbiturates act directly on the spinal cord, depressing both monosynaptic and polysynaptic reflexes. Propanediols and benzodiazepines act primarily on the descending facilitatory influence of the brainstem. Reduction of this influence depresses spinal polysynaptic but not monosynaptic reflexes. Biochemical studies suggest that barbiturates may act by antagonizing synaptic excitation induced by glutamate. Benzodiazepines may act by enhancing presynaptic inhibition mediated by GABA. The mechanism of action of propanediols is unknown.
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PMID:Neuropharmacology of sedatives and anxiolytics. 3 29

Benzodiazepines are generally well tolerated (compared to barbiturates or antidepressants, their side-effects are milder). They may be used safely, their toxicity is low. Benzodiazepine overdosage may be lethal only if the drug is taken simultaneously with other drugs or alcohol. They act primarily through inhibiting the GABA system, their anxiolytic and sedative effects are of primary importance from the psychiatric aspect. Their classification is based on the difference in their receptor affinity (potency) and kinetics. Derivatives of low, medium and high potency are known. The introduction of high potency benzodiazepines in psychiatry has increased the therapeutic means. The major field of indication of benzodiazepine therapy is DSM-III anxiety disorders and insomnias but they may be successfully used in the treatment of manic conditions, schizophrenia, delirium tremens, clinical conditions accompanied by anxiety-depression, acute restlessness, neuroleptic-induced acute distonias, and akathisias. Even if therapeutic doses are used, tolerance to benzodiazepines may develop after some weeks of therapy. The general withdrawal symptoms are not severe, but the rebound symptoms often hinder the discontinuance of the drug or the reduction of doses. When prescribing benzodiazepines the risk of long-term therapy and the prevention of the development of drug addiction have to be considered.
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PMID:Use of benzodiazepines in psychiatry. 181 22

Sixty-one pediatric patients (12-229 months of age) with refractory epilepsy were treated with vigabatrin [gamma-vinyl GABA (GVG)] in a 16-week, single-blind, add-on, placebo-controlled trial. Twenty-three patients (38%) showed a reduction of more than 50% in seizure frequency; 12 patients (20%) experienced a seizure increase; and the remaining 26 did not show significant differences between placebo and GVG treatment. Among the 216 patients who entered the long-term phase after having experienced more than 50% decrease in seizure frequency, 14 continued with the same degree of improvement after 2-11 months of follow-up (mean 7.7). GVG was particularly efficient in cryptogenic partial epilepsy. Conversely, nonprogressive myoclonic epilepsy tended to be aggravated. Agitation was the most commonly observed side effect, mainly at onset of therapy in mentally retarded patients, but was easily reversed by dose reduction. GVG is a promising drug in the treatment of refractory epilepsies of childhood.
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PMID:Vigabatrin in the treatment of childhood epilepsies: a single-blind placebo-controlled study. 250 84

Intrathecal administration of glycine (strychnine) or GABA (bicuculline) but not opioid (naloxone), adrenergic (phentolamine) or serotonin (methysergide) receptor antagonists resulted in a dose-dependent organized agitation response to light tactile stimulation. This effect was maximally evoked by oscillating but not continuous stimulation applied to a dermatome corresponding to the levels of spinal cord acted upon by the intrathecal antagonist. Similar results were observed in chloralose-urethane anesthetized rats in which tactile stimulation evoked hypertensive responses following local tactile stimuli. The effects were only mildly depressed by even high doses of spinal morphine or DADL and not at all by ST-91 or baclofen. In contrast, intrathecal injections of glutamate receptor antagonists resulted in a dose-dependent depression of the strychnine evoked hyperesthesia with the ordering of activity being MK-801, AP-5, kynurenic acid, SKF10047 and ketamine. At doses below those which produced motor dysfunction, however, these agents had no effects on the hot-plate response latency. These data emphasize that low threshold afferent input is likely subject to an ongoing modulation, the loss of which results in a miscoding of the afferent stimulus yielding a pain relevant message. The lack of effect of agents having a powerful effect on somatic pain stimuli and the converse effects of glutamate receptor antagonists on the strychnine hyperesthesia at doses which do not affect the somatic pain response indicate discriminable processing systems, the characteristics of which resemble the clinical phenomenon observed in patients suffering from sensory dysesthesia following central and peripheral horn injury.
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PMID:Behavioral and autonomic correlates of the tactile evoked allodynia produced by spinal glycine inhibition: effects of modulatory receptor systems and excitatory amino acid antagonists. 254 67

Movement abnormalities in neuroleptic-treated, psychiatric patients are classified as (a) initial syndromes, including dystonia, parkinsonism, and hyperkinetic abnormalities such as initial dyskinesia (ID) and akathisia, all of which are related to the neuroleptic dose and can be considered as overdose phenomena; (b) tardive syndromes, mainly the classic tardive dyskinesia (TD) syndrome, more seldom tardive akathisia and tardive dystonia, which may all develop or aggravate after withdrawal of neuroleptic treatment; and (c) age-related, spontaneous dyskinesia, akathisia, and dystonia, and schizophrenia-related, hyperkinetic, often stereotyped, movements and restlessness. ID and TD can occur simultaneously, and may depend, at least partially, on identical mechanisms. The pathophysiology of TD is still not clear, and the traditional dopamine (DA) hypersensitivity model seems inadequate. Animal experiments suggest that blockade of some DA receptors in the brain (e.g., in ventromedian striatum) may counteract hyperkinesia and produce parkinsonism, while a concomitant blockade of other similar receptors in other brain regions (e.g., in anterodorsal striatum) may aggravate movements. This offers an explanation for the concomitant occurrence of parkinsonism and hyperkinetic movement abnormalities (ID and akathisia) relatively early in a neuroleptic treatment, and may also contribute to the understanding of the pathophysiology of TD. It is concluded that pathophysiologically TD is a heterogeneous syndrome depending on a subtle balance between several neurotransmitters in the brain, including DA receptor blockade and hypersensitivity of DA and GABA receptors.
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PMID:Pathophysiological mechanisms underlying tardive dyskinesia. 286 Jun 66

CSF GABA levels were not significantly different in a group of drug-free psychotic patients compared to a group of psychotic patients at two points during haloperidol treatment or a neurological comparison group. In the untreated group, CSF GABA was significantly negatively correlated with clinical ratings of anxiety and agitation. Early in haloperidol treatment CSF GABA was significantly positively correlated with CSF HVA.
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PMID:CSF GABA in psychotic disorders. 677

Vigabatrin (VGB) is a recently-released antiepileptic drug which works by a clearly-defined mechanism of action: inhibition of GABA transaminase leading to an elevation of brain GABA concentration. It has been proven effective, mainly as an add-on agent, in complex partial and secondarily generalized seizures in both adults and children as well as in infantile spasms in both short and long-term controlled studies. World-wide experience now includes over 150,000 patients exposed to the drug. VGB has a favorable pharmacokinetic profile since it has little protein-binding, is mainly excreted unchanged by the kidney and has a long effective half-life allowing once or twice daily dosing. It is generally well-tolerated with very few cognitive effects but may cause significant behavioral side effects such as agitation, irritability, depression or psychosis in approximately 2-4% of cases. Mild weight gain and possible exacerbation of absence and myoclonic seizures are other reported adverse effects. The role of VGB in other childhood epileptic syndromes apart from West syndrome is still being defined.
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PMID:Vigabatrin. 895 Dec 15

Psychopathological and neurological adverse drug reactions (ADR) have been repeatedly reported during treatment with gyrase inhibitors (fluorquinolones). Results of earlier studies indicated a high risk for ADR especially in the elderly with high dosage medication, psychiatric history and renal dysfunction. The pathophysiological mechanisms involved in the development of adverse CNS effects are not completely understood. GABA-ergic and monoaminergic mechanisms might play a major part. In a retrospective study conducted by the authors 4189 reports of consultant psychiatric examinations were analyzed. In 29 patients the suspicion of psychopathological ADR during treatment with ofloxacin or ciprofloxacin was documented. Psychopathological findings included delirious states, paranoid, depressive and manic syndromes, agitation, sleep disturbances, sopor and stupor. In elderly patients delirious and paranoid syndromes were predominant, whereas affective disturbances occurred more often in younger patients. In most cases multiple morbidity, liver or kidney diseases, simultaneous treatment with other antibiotics and immunosuppressants, former psychiatric disorders or psychosocial stress factors were present. The results of the study, methodological problems, aspects of risk analysis and implications for medical treatment are discussed.
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PMID:[Psychopathological syndromes in treatment with gyrase inhibitors]. 913 19

Intrathecal strychnine (glycine antagonist) or bicuculline (GABA(A) antagonist) yields a touch-evoked agitation that is blocked by N-methyl-D-aspartate receptor antagonism. We examined the effects of intrathecal strychnine and bicuculline on touch-evoked agitation and the spinal release of amino acids. Fifty-two Sprague-Dawley rats were prepared under halothane anesthesia with a lumbar intrathecal catheter and a loop dialysis catheter. Four days after implantation, rats were randomized to receive an intrathecal injection of N-methyl-D-aspartate (3 microg), strychnine (3 microg) or bicuculline (10 microg), or a combination of N-methyl-D-aspartate with bicuculline or strychnine. The agitation produced by brief light tactile stroking of the flank (tactile allodynia), and the spontaneous spinal release of glutamate, taurine and serine was measured. Intrathecal N-methyl-D-aspartate, strychnine and bicuculline produced similar touch-evoked allodynia. Intrathecal bicuculline and N-methyl-D-aspartate alone evoked a transient spinal release of glutamate and taurine, but not serine, in the 0- 10 min sample, while strychnine did not affect spinal transmitter release at any time. As GABA(A) but not glycine receptor inhibition at equi-allodynic doses increases glutamate release, while the allodynia of both is blocked by N-methyl-D-aspartate receptor antagonism, we hypothesize that GABA(A) sites regulate presynaptic glutamate release, while glycine regulates the excitability of neurons postsynaptic to glutamatergic terminals.
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PMID:Characterization of spinal amino acid release and touch-evoked allodynia produced by spinal glycine or GABA(A) receptor antagonist. 1067 Apr 45

Valproate is currently one of the most frequently prescribed drugs in schizophrenia spectrum disorders. However, surprisingly little is known from controlled studies. Also, no review articles are available. Here, we summarize basic and clinical research on valproate and its application for treatment in schizophrenia spectrum disorders. The molecular and physiological effects of valproate are outlined. It is discussed how the effects of valproate on the cellular level involving serotonin, GABA, glutamate, sodium-channels, membrane fluidity and RNA-expression may account for its clinical effect in schizophrenia spectrum patients. The target symptoms are a reduction of psychomotor agitation and aggression, possibly reflecting a drug effect on temporal lobe pathology, which is considered to be involved in the etiology of schizophrenic illness.
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PMID:Valproate and the symptomatic treatment of schizophrenia spectrum patients. 1107 Oct 20


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