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)

Nausea and vomiting are serious problems for patients receiving cancer chemotherapy. Dopamine receptor and cholinergic receptor antagonism have been the target mechanism for agents used to combat drug-induced nausea and vomiting; more recently, blockade of serotonin receptors has been used for this indication. Current therapies are limited by extrapyramidal adverse effects, as well as drowsiness, sedation, respiratory depression, and cardiac effects. Ondansetron is an investigational serotonin antagonist that has documented effectiveness for cancer chemotherapy-induced emesis. Ondansetron appears to be well tolerated, with the possible exception of headaches and transient increases in liver enzymes. No extrapyramidal toxicities have been reported with this agent. While ondansetron looks promising, further studies are needed to fully define its role as an antiemetic.
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PMID:Ondansetron: a new entity in emesis control. 214 59

This study was undertaken to investigate the effects of activating dopamine receptors in accumbens and prefrontal cortex on self-stimulation behavior in the medial forebrain bundle. The experiments were carried out in rats chronically implanted with one stimulating electrode in medial forebrain bundle and two bilaterally-placed cannulas for giving injections into accumbens or prefrontal cortex. After completion of training, animals classified as responders and non-responders were given drug tests. The non-responders were tested to determine the effects of the treatment on motor activity. The self-stimulation task involved the depression of a lever to obtain a stimulus of 0.25 s duration, 60 Hz sine waves applied to the medial forebrain bundle. Dopamine receptor activation in accumbens or prefrontal cortex was induced with bilateral injections in these structures of a mixture containing 5 mg dopamine, 10 mg d-amphetamine sulfate and 5 mg pargyline mixed in 0.5 ml saline containing 0.1% ascorbic acid (dopamine + d-amphetamine sulfate + pargyline, the cocktail). Each injection was of 2 microliters/side, yielding a concentration of 20 micrograms of dopamine, 40 micrograms of d-amphetamine sulfate and 20 micrograms of pargyline/injection. The bilateral injections were given immediately before the self-stimulation session which lasted 12 h, starting in late afternoon. The effects of saline containing the ascorbate were determined in control sessions. Saline injected bilaterally in accumbens or prefrontal cortex of self-stimulators or non-self-stimulators had no effects on the response-rate of self-stimulators or on the gross motor activity of non-responders. In contrast, the cocktail of dopamine + d-amphetamine sulfate + pargyline injected in accumbens of self-stimulators induced a complex response which included first a facilitation, then a prolonged suppression and then again one or two episodes of facilitation interspersed with periods of suppression of self-stimulation and then a return to baseline rats. The same cocktail of dopamine + d-amphetamine sulfate + pargyline injected bilaterally in accumbens of non-self-stimulators resulted also in a complex response including as a first component a facilitation of responding, but the complex effect was of shorter duration and lower magnitude, never raising the rate of lever-pressing to levels meeting self-stimulation criteria. The same cocktail of dopamine + d-amphetamine sulfate + pargyline injected in prefrontal cortex of self-stimulators simply attenuated or suppressed responding, and the effect lasted for most of the session. The same effect was seen in non-self-stimulators indicating a decrease in gross motor activity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Enhanced dopamine receptor activation in accumbens and frontal cortex has opposite effects on medial forebrain bundle self-stimulation. 219 40

Concentrations of several large neutral amino acids (LNAA) were earlier shown to be low, especially in brain, in rats fed a low protein diet containing a mixture of LNAA analogues. The purpose of this study was to learn if individual analogues would induce similar effects. Four hours after first feeding one meal containing norleucine, norvaline, alpha-aminophenylacetic acid, or alpha-aminooctanoic acid, concentrations of branched-chain amino acids were low in plasma, brain, liver and muscle; tyrosine and phenylalanine were more effectively reduced in brain than in other tissues. Lysine and arginine concentrations were low in brains of rats fed the basic amino acid analogue, homoarginine; concentrations of large and small neutral amino acids were unchanged. Dopamine was not low in brains having low tyrosine levels; serotonin was low in rats receiving alpha-aminooctanoate, the only analogue associated with a significant depression in brain tryptophan. The results suggest that the analogues have differing abilities to alter concentrations of tissue components. Decreases, especially in brain amino acid concentrations, may result from selective competition by analogues of a given transport class with natural amino acids transported from blood into brain by the same system.
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PMID:Tissue amino acids in rats fed norleucine, norvaline, homoarginine or other amino acid analogues. 242 57

Dopamine and serotonin systems are morphologically interconnected in the midbrain. Several studies have also demonstrated a functional relationship between these two monoamine systems. Concentrations of their metabolites, 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA), consistently correlate with one another in human cerebrospinal fluid. Previous studies of the effects of antidepressants on the dopamine and serotonin systems have focused on the two systems in isolation without considering the interactions between the two. One way of taking this interaction into account may be to form a ratio of dopamine and serotonin measures. The present study measured HVA and 5HIAA in cerebrospinal fluid of 31 patients with depression and 12 patients with Alzheimer's disease before and after treatment with a variety of antidepressant drugs. The ratio of HVA/5HIAA was able to discriminate much more powerfully between effects of different drugs than HVA or 5HIAA examined separately.
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PMID:The effects of antidepressants on the cerebrospinal fluid homovanillic acid/5-hydroxyindoleacetic acid ratio. 244 15

The effect of ammonia infusion on monoamine metabolism was studied in the rat brain. Seven days after portocaval shunt (PCS) or sham operation animals were infused with ammonia or saline. Brain metabolism of serotonin and norepinephrine was studied after injection of a decarboxylase inhibitor (m-hydroxybenzylhydrazine, NSD 1015) which blocks the conversion of 5-hydroxytryptophan to serotonin and dihydroxyphenylalanine to dopamine. Neurologic testing was conducted before killing. Plasma and brain amino acids were measured. PCS animals infused with ammonia were in deep coma after 6 h infusion, whereas sham-operated animals were virtually unaffected. Brain amino acid analyses demonstrated increased concentrations of the aromatic amino acids and a tenfold increase in glutamine. Serotonin metabolism was diminished after 6 h. Dopamine synthesis was normal, but norepinephrine levels were low after 6h. The study suggests that hyperammonemia in PCS rats results in a depression of the serotonin synthesis rate in accordance with two previous studies but in contrast to previous hypotheses on the regulation of serotonin metabolism.
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PMID:The effect of ammonia infusion on brain monoamine metabolism in portacaval-shunted rats. 247 Dec 38

Neurotransmitter receptor binding and Na+, K+-ATPase activity were examined in the brains of six rats exposed to 7 days of microgravity during the flight of Spacelab 3. The same variables were examined in a group of six ground control rats. 5-HT1 receptor number in the hippocampus was significantly elevated by exposure to the microgravity environment, and cortical sodium-potassium pump activity was significantly depressed. A marginal depression in dopamine D-2 binding in the striatum was noted. Dopamine and 5-HT binding in a wide variety of other central regions, in addition to GABAA, muscarinic acetylcholine, adenosine A1, and opiate receptor binding, and adrenoceptor binding, was unaffected by microgravity exposure.
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PMID:Effects of microgravity on brain neurotransmitter receptors. 254 43

Excitatory junction potentials (e.j.ps) evoked by nerve stimulation with 15 pulses at 1 Hz were recorded from muscle cells of rabbit isolated jejunal arteries. LY 171555 1 mumol/l, SKF 38393 10 mumol/l, dopamine 10 mumol/l and clonidine 0.1 mumol/l depressed all e.j.ps in the train. The percentage inhibition was inversely related to the number of pulses. S- and R-sulpiride, 10 mumol/l, domperidone 1 mumol/l, SCH 23390 1 mumol/l and rauwolscine 1 mumol/l did not change, or even depressed the first e.j.ps. Of these compounds only S- and R-sulpiride, 10 mumol/l and rauwolscine 1 mumol/l facilitated the late e.j.ps. The percentage facilitation increased with the number of pulses until a maximum was reached; rauwolscine 1 mumol/l had the largest effect. S- and R-sulpiride, 10 mumol/l, as well as domperidone 1 mumol/l antagonized the action of LY 171555 1 mumol/l. S-Sulpiride was more potent than its R-isomer. SCH 23390 1 mumol/l and rauwolscine 1 mumol/l blunted the effect of SKF 38393 10 mumol/l. Rauwolscine 1 mumol/l slightly reduced the inhibition by dopamine 10 mumol/l; S-sulpiride 10 mumol/l was antagonistic only in the presence of rauwolscine 1 mumol/l. When rauwolscine 1 mumol/l, prazosin 0.1 mumol/l, propranolol 1 mumol/l and cocaine 10 mumol/l was added to the medium, dopamine 10 mumol/l continued to produce the same depression of e.j.ps, as in the absence of these compounds. Under such conditions S-sulpiride 10 mumol/l also counteracted dopamine 10 mumol/l. Rauwolscine 1 mumol/l prevented the effect of clonidine 0.1 mumol/l. The antagonists were not absolutely selective against only one type of agonist. We suggest that both presynaptic DA2- and postsynaptic DA1-receptors are present in rabbit jejunal arteries. The activation of either receptor-type may depress the e.j.ps. Dopamine interferes with neuroeffector transmission due to alpha 2-adrenoceptor agonist properties; its DA2-effect is unmasked only after alpha 2-adrenoceptor blockade. There was no evidence for a co-transmitter function of dopamine.
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PMID:Presynaptic dopamine DA2-receptors in rabbit jejunal arteries. An electrophysiological study. 257 71

Self-reported levels of pain, anxiety, and depression, and plasma levels of beta-endorphin, epinephrine, norepinephrine, dopamine, and serotonin were measured in 19 arthritic pain patients before and after hypnosis designed to produce pain reduction. Correlations were found between levels of pain, anxiety, and depression. Anxiety and depression were negatively related to plasma norepinephrine levels. Dopamine levels were positively correlated with both depression and epinephrine levels and negatively correlated with levels of serotonin. Serotonin levels were positively correlated with levels of beta-endorphin and negatively correlated to epinephrine. Following hypnotherapy, there were clinically and statistically significant decreases in pain, anxiety, and depression and increases in beta-endorphin-like immunoreactive material.
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PMID:Biochemical correlates of hypnoanalgesia in arthritic pain patients. 315 43

To explain some mechanisms of the peripheral action of dopamine experiments were carried out on anesthetized rabbits in which the blood flow in calf muscles was measured during rest and during evoked twitches, using the method of 133Xe clearance of Lassen et al.; the arterial blood pressure and ECG were simultaneously recorded. Dopamine reduced the blood flow, particularly after a muscular effort. That effect of dopamine was not blocked by the alpha- and beta-adrenoceptor antagonists phentolamine and propranolol, the dopamine receptor antagonist haloperidol, or by the agent blocking sympathetic nerve endings compound BW392C60. Only low doses of dopamine given after propranolol pretreatment caused an increase in the blood flow. Dopamine depressed the arterial blood pressure, particularly the diastolic one. Pretreatment with phentolamine and haloperidol did not antagonize that effect, while pretreatment with propranolol or BW392C60 abolished or reversed the action of dopamine. The depression by dopamine of the blood flow in an important area of skeletal muscles indicates that part of the circulating blood may be shifted to other vascular beds, e.g. to the viscero - renal one.
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PMID:The effect of dopamine on blood flow in skeletal muscles. 323 64

Dopamine receptor blocking drugs, commonly used in the treatment of involuntary movements, may cause potentially serious adverse effects, including tardive dyskinesia. Tardive dyskinesia has not been reported with tetrabenazine, a dopamine-depleting drug. We report a follow-up in 217 patients treated with tetrabenazine for about 18 months (range, 1 to 80). The response was rated on a scale of 0 to 5 (1 = marked improvement, 4 = no response, 5 = worsening). The mean effect from tetrabenazine was rated as follows: 2.3 in 44 patients with tardive dyskinesia, 2.6 in 15 with tardive dystonia, 2.6 in 10 with Huntington's disease, 2.7 in 17 with Gilles de la Tourette's syndrome, 2.8 in 19 with generalized dystonia, 2.8 in 57 with Meige's syndrome, and 3.4 in 25 with other focal dystonias. Twenty-two patients with a variety of unusual movement disorders had a mean effect of 2.9. Parkinsonism occurred as a side effect in 53 patients, sedation in 28, depression in 23, anxiety in 16, insomnia in 11, and akathisia in 10. The choreatic movement disorders are most amenable to tetrabenazine therapy, but tardive and idiopathic dystonia may also be responsive. Tetrabenazine is an effective and relatively safe drug for a variety of hyperkinetic movement disorders.
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PMID:Tetrabenazine therapy of dystonia, chorea, tics, and other dyskinesias. 327 37


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