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)

Research was conducted upon 28 patients with a diagnosis of endogenous depression after their pharmacological treatment with imipramine or chlorimipramine. The investigation considered the interrelationship between psychophysiological parameters (heart rate, respiration rhythm, postural muscular tension) and the indices of the cholinergic and adrenergic systems (kinetic parameters of choline transport in the blood; Vmax, the activity of plasmic pseudocholinesterase, Che; blood acetylcholinesterase AChE, monoaminoxidase in blood platelets, MAO; and dopamine beta hydroxylase DBH). The results indicate that during relapse of endogenous depression there occurs an imbalance in the cholinergic-adrenergic systems which may be the result of some somatic symptoms typically found in the depression syndrome. The appearance, after pharmacotherapy, of a correlation between the indices of the activity of the cholinergic system with the respiratory rhythm suggest that the part played by the cholinergic mechanism in the regulation of autonomic processes normalizes itself during the course of successful therapy. The appearance of characteristic correlations between the activity of the cholinergic and adrenergic systems and the psychophysiological parameters in the presence of relatively low psychological stress seems to accompany successful treatment with imipramine and chlorimipramine.
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PMID:[Psychophysiological characteristics and metabolic indices of neurotransmitter metabolism in patients ill with endogenous depression]. 130 98

7-Bromo-(3a,5-cis)-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethyl-pyrrolo[2,3- 6]indol-5-ol fumarate (HP 736) is a novel opioid analgesic. In vitro, HP 736 displaces [3H]dihydromorphine (IC50 = 8.3 x 10(-10) M) and [3H]bremazocine (IC50 = 7.4 x 10(-8) M) from mu and kappa opioid receptors, respectively, and displays modest acetylcholinesterase inhibitory activity (IC50 = 4.0 x 10(-5) M). The in vivo antinociceptive activity of HP 736 was found to be comparable to morphine in the modified Haffner's tail clip assay in mice and the D'Amour-Smith tail flick assay in rats. Moreover, these analgesic effects were found to be completely antagonized by the administration of the narcotic antagonist naloxone. A major liability of opioid analgesics such as morphine is the potential to cause cardiorespiratory depression. HP 736 (2, 4 and 10 mg/kg, i.v.) was found to cause significantly less respiratory depression in the anesthetized dog when compared to equivalent doses of morphine. At 10 mg/kg, morphine caused a 48% reduction in arterial oxygen partial pressure (PaO2) (-42.3 +/- 2.5 mm Hg) and a 52% increase in arterial carbon dioxide partial pressure (PaCO2) (21.0 +/- 3.4 mm Hg). In contrast, the same dose of HP 736 produced no significant decrease in PaO2, but did cause a slight 19% increase in PaCO2 (8.2 +/- 1.3 mm Hg), which was significantly less than the response seen after morphine treatment. It was found that pretreatment of the dogs with atropine sulfate (1 mg/kg, i.v.) "unmasked" the respiratory depressant activity of HP 736 (2 mg/kg, i.v.), indicating that the acetylcholinesterase inhibitory activity of the compound may contribute to its reduced cardiorespiratory liability. Finally, in confirmatory experiments conducted in conscious goats, HP 736 (0.5 mg/kg, i.v.) was found to stimulate pulmonary ventilation, increase PaO2 and oxygen consumption (+40%) and decrease PaCO2 with an overall stimulatory effect on the metabolic rate. In contrast, the same dose of morphine decreased metabolic rate, reduced pulmonary ventilation (-20%) and PaO2 and increased PaCO2. Overall, the results of these studies indicate that HP 736 is a potent opioid analgesic which appears to lack significant cardiorespiratory depressant activity.
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PMID:Cardiorespiratory effects of the novel opioid analgesic HP 736 in the anesthetized dog and conscious goat. 134 66

The urinary excretion rates of diethyl phosphate and diethyl phosphorothioate and changes in blood cholinesterase activities were studied in fifteen persons self-poisoned either by the organophosphorus pesticide quinalphos (twelve persons) or by chlorpyrifos (three persons). The organophosphate poisoning was always indicated by a significant depression of serum and/or red blood cell cholinesterase activities. The return of serum cholinesterase activity in the range of referent values took more than 30 days and had a different course in different persons. The most rapid increase in red blood cell acetylcholinesterase activity was noted within 24 h after the first treatment with oximes Pralidoxime and/or HI-6. None of the spot urine samples, collected daily after admission of persons to hospital, contained measurable quantities of the parent pesticide. There was no correlation between the maximum concentration of total urinary diethylphosphorus metabolites normalized to creatinine and the initial inhibition of blood cholinesterase activities measured in samples collected on the day of admission to hospital. The excretion of metabolites followed the kinetics of a biphasic reaction. The half-time of urinary metabolites concentration decrease in the fast excretion phase in quinalphos poisoned persons was 5.5-14.2 h (eight persons) and 26.8-53.6 h (four persons) and in chlorpyrifos poisoned persons 3.5-5.5 h. The half-time for the slow excretion phase ranged from 66.5 to 127.9 h in all persons and for both compounds. For a given person, the rates of excretion of diethyl phosphate and diethyl phosphorothioate were about the same. However, in quinalphos poisoned persons the proportions of single metabolites in total diethylphosphorus metabolites varied with the initial maximum concentration of total metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Urinary excretion of diethylphosphorus metabolites in persons poisoned by quinalphos or chlorpyrifos. 137 16

An extract with cholinergic activities was isolated from instant regular and decaffeinated coffees and purified. Intravenous injection of this cholinomimetic extract of coffee produced an abrupt depression in blood pressure and heart rate, changes that were distinct from those of known components of coffee, including caffeine, trigonelline, catechin, and chlorogenic acid. Pretreatment of the animals with naloxone, propranolol, isobutylmethylxanthine, hexamethonium bromide, and hemicholinium-3 chloride or bilateral vagotomy did not affect the cardiodepressive effects of the extract, whereas atropine completely abolished them. Direct injection of the cholinomimetic extract of coffee (20-100 micrograms) into the periaqueductal gray area of the midbrain did not produce any cardiovascular effect. However, the extract of coffee did cause relaxation of isolated rat and rabbit aortic ring preparations that were contracted under norepinephrine. The cholinomimetic extract did not inhibit purified acetylcholinesterase. This pharmacologic profile indicates that the cholinomimetic extract of coffee acts as a direct muscarinic agonist.
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PMID:Cholinomimetic compound distinct from caffeine contained in coffee. II: Muscarinic actions. 140 78

Wistar rat pups (female) were exposed to methylparathion (MPTH) by gastric intubation in single doses, or in a chronic regimen of different durations. A single dose of 1 mg MPTH/kg body weight in 15-day-old pups caused a significant decrease of acetylcholinesterase (AChE) activity in cerebellum (CE), motor cortex (MC) and brain stem (BS). The effect began to appear in about 20 min after administration, the peak effect was attained in 120 min and later on this waned off completely by 24 h. The effect was similar in young (15 days) and in adult (70 days) rats. A single dose of 0.2 mg MPTH/kg in 15 day old pups caused a reduction of AChE activity only in the BS, while a 0.1 mg MPTH/kg single dose given to 15-day-old pups caused no effect even in seven regions of the brain examined. Effect of low dose chronic administration of MPTH on AChE activity was also studied in CE, MC, BS, hippocampus (HI), striatum-accumbens (SA), spinal cord (SC) and also in the hypothalamus (HY). Administration of 0.1 mg MPTH/kg from second day to 15 days of age caused significant reduction of AChE activity in only 2 of the 7 brain regions studied. Administration of double the dose (0.2 mg MPTH/kg) and for a longer duration (2nd day to 150 days of age), caused a depression in all the brain regions studied. In all these regions, the levels of NA, DA and 5HT did practically not change. The results suggest that chronic consumption of MPTH leads to a moderate decrease of AChE activity in several brain regions.
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PMID:Effect of chronic consumption of methylparathion on rat brain regional acetylcholinesterase activity and on levels of biogenic amines. 145 21

Biochemical responses of animals to environmental chemicals (biochemical biomarkers) can give measures of exposure, and sometimes also toxic effect. They are particularly valuable where they can be used to measure the toxic effects of chemicals in the field, employing non-destructive sampling methods. Measurements of exposure are useful in the case of non-persistent chemicals (e.g. organophosphorus, carbamate, or pyrethroid insecticides) which are difficult or impossible to detect by chemical analysis. They can also be useful to provide an integrated measure of the level of exposure to a group of related chemicals. Biochemical biomarkers are likely to provide a measure of toxic effect, where they are based upon a molecular mechanism which underlies toxicity. A widely-used biochemical biomarker is cholinesterase depression, which may involve destructive sampling (brain acetylcholinesterase) or non-destructive sampling (serum butyrylcholinesterase). For genotoxic chemicals, techniques which measure DNA damage (e.g. detection of DNA adducts) provide a powerful tool in measuring environmental effects. The detection of biochemical changes caused by anticoagulant rodenticides (e.g. abnormal levels of clotting proteins in blood) provides another example of this approach. In general, the development of simple, sensitive, and specific assays that are 'user-friendly' would open the way for much wider use of biochemical biomarkers in environmental monitoring.
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PMID:Biochemical responses as indicators of toxic effects of chemicals in ecosystems. 147 Dec 5

Physostigmine was originally isolated from the Calabar Bean, which was used for ordeal by poison in West Africa. The main alkaloid was isolated in 1864. It acts through inhibition of acetylcholinesterase, and has been of major importance in elucidating the kinetics and configuration of the enzyme. Physostigmine has been important for our understanding of neurohumoral chemical transmission, and in mapping the cholinergic nerves. It was the first antagonist to curare, and has been widely used for various therapeutic purposes. Today it has been largely replaced by more efficient and safe drugs. It is still used as an antidote to poisoning from various psychopharmacological drugs, and to treat postoperative somnolence and respiratory depression. It is considered a potent antidote to organophosphorous poisoning and is used experimentally to treat Alzheimer's disease.
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PMID:[Development of physostigmine from a poisonous plant to an antidote. One of the most important drugs in the development of modern medicine?]. 157 14

Nine fairways of a golf course located in Bellingham, Washington were treated with diazinon AG500 at a target application rate of 2.2 kg active ingredient (AI) per ha. The chemical application with a "boomless" sprayer resulted in a variable distribution of diazinon residues on the turf (associated with a deep thatch layer) that ranged from 1.0 to 6.2 kg AI/ha. The diazinon-treated turf was irrigated with 1.3 cm of water immediately following application. The post-irrigation diazinon residue levels ranged from 100 to 333 ppm (mean = 209; SD = 88; n = 8). These residue levels were higher than expected based on results of turf studies in other regions of the United States. Eighty-five American wigeon (Anas americana) died after grazing on one treated fairway on the day of application following irrigation. The brains of all 85 wigeon were analyzed for acetylcholinesterase (AChE) activity. Wigeon that died on the study area (n = 85) showed 44% to 87% depression of AChE (mean = 76%; SD = 7.1%) when compared to control wigeon (n = 3; AChE Activity = 1.86) AChE levels. Upper GI tract contents of 15 of the 85 dead wigeon contained 0.96 to 18.1 ppm diazinon. Extensive carcass searches revealed no other avian mortality attributable to diazinon toxicity on the treated study area. Although initial post-irrigation diazinon residues in grass samples were higher than expected, diazinon levels in grass samples on day seven post-application had declined to an average of 29 ppm. American wigeon appear to be vulnerable to exposure to diazinon.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:American wigeon mortality associated with turf application of diazinon AG500. 160 78

Slices of human neocortex prelabelled with [3H]choline were superfused and stimulated electrically (3 Hz, 2 ms, 24 mA) in order to investigate the autoreceptor-mediated modulation of acetylcholine (ACh) release. The concentration-response curve of the muscarinic agonist oxotremorine (pKd = 6.76 +/- 0.06), which was equipotent to ACh, was shifted to the right in a parallel manner by atropine (pA2 = 8.56 +/- 0.11), as evaluated by non-linear regression analysis. Calculation of the biophase concentration of ACh showed that no ACh could be assumed to be present under these conditions, whereas following inhibition of the acetylcholinesterase by physostigmine (0.1 microM) a biophase concentration of 10(-6.89 +/- 0.11) M was estimated. The depression of ACh release due to physostigmine and tacrine, another anticholinesterase, was antagonized by atropine. When the autoinhibition was operative atropine and the M2 subtype specific muscarinic antagonists, AF-DX 116 and methoctramine, significantly increased the release of ACh whereas the 'facilitatory' effects of the M1 and M3-specific drugs, pirenzepine and hexahydrosiladifenidol, were not significant. Although different disinhibitory effects of the subtype-specific antagonists were found, they did, however, not show a pattern which would allow a clear characterisation of the subtype of muscarinic receptor associated with the autoreceptor. The release of ACh from neocortex tissue of the (non-demented) neurosurgical patients decreased with their age. This finding is consistent with the hypothesis that the normal aging process resembles a delayed and attenuated disease process of senile dementia of Alzheimer's type.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The autoinhibitory feedback control of acetylcholine release in human neocortex tissue. 161 39

The ability of acetylcholinesterase from fetal bovine serum (FBS AChE) to protect against soman, a highly toxic organophosphorus (OP) compound, was tested in rhesus monkeys. Intravenous administration of FBS AChE produced a minimal behavioral effect on the serial probe recognition task, a sensitive test of cognitive function and short-term memory. Pharmacokinetic studies of injected FBS AChE indicated a plasma half-life of 40 hr for FBS AChE in monkeys. Both in vitro and in vivo titration of FBS AChE with soman produced a 1:1 stoichiometry between organophosphate-inhibited FBS AChE and the cumulative dose of the toxic stereoisomers of soman. Administration of FBS AChE protected monkeys against the lethal effects of up to 2.7 LD50 of soman and prevented any signs of organophosphate intoxication, e.g., excessive secretions, respiratory depression, muscle fasciculations, or convulsions. In addition, monkeys pretreated with FBS AChE were devoid of any behavioral incapacitation after soman challenge, as measured by the serial probe recognition task. Compared to the current multicomponent drug treatment against soman, which does not prevent the signs or the behavioral deficits resulting from OP intoxication, use of FBS AChE as a single pretreatment drug provides significantly effective protection against both the lethal and the behavioral effects of soman.
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PMID:Protection of rhesus monkeys against soman and prevention of performance decrement by pretreatment with acetylcholinesterase. 163 92


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