UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many of the drugs used in anesthesia and intensive care may cause blockade of the central cholinergic neurotransmission. Acetylcholine is of significance in modulation of the interaction among most other central transmitters. The clinical picture of the central cholinergic blockade, known as the central anticholinergic syndrome (CAS), is identical with the central symptoms of atropine intoxication. This behaviour consists of agitation including seizures, restlessness, hallucinations, disorientation or signs of depression such as stupor, coma and respiratory depression. Such disturbances may be induced by opiates, benzodiazepines, phenothiazines, butyrophenones, ketamine, etomidate, propofol, nitrous oxide, and halogenated inhalation anesthetics as well as by H2-blocking agents such as cimetidine. There is an individual predisposition for CAS--but unpredictable from laboratory findings or other signs. Reports of postanesthetic occurrence of the CAS requiring treatment are not unanimous, varying between 1 and 40%. Differential diagnosis of the CAS includes disorders of glucose and electrolyte metabolism, severe hormonal imbalance, respiratory disorders (hypoxia, hypercarbia), hypothermia, hyperthermia and neuropsychiatric diseases (cerebral hypoxia, stroke, catatony, acute psychosis). The CAS may considerably impair the postanesthetic period especially when agitation is prevalent, which may endanger the patient or the surgical results. The diagnosis is confirmed ex iuvantibus by the sudden increase in the acetylcholine level in the brain. This is achieved with physostigmine, a cholinesterase inhibitor able to easily cross the blood-brain barrier. Its peripheral muscarinic effects are minimal. Postanesthetic CAS can be prevented by administration of physostigmine during the anesthesia procedure. During intensive care (IC), agitated forms of CAS may occur in patients undergoing mechanical ventilation, particularly during prolonged high-dose sedation. Artificial ventilation of such patients becomes very difficult and muscle relaxation may be necessary. In these cases of IC-CAS, physostigmine is of value and has proven beneficial during weaning from mechanical ventilation. Dealing with the CAS for more than a decade has improved knowledge of the central cholinergic transmission. For example, it can be said that CAS occurs alongside general anesthesia, being no more than a frequent side-effect. Furthermore, acetylcholine is involved in nociception through the endorphinergic and the serotoninergic systems. There is a close relation between the central cholinergic transmission and actions of nitrous oxide. Moreover, cholinergic transmission is involved in withdrawal from (among others) alcohol, opiates, hallucinogens and nitrous oxide. In some intoxications with psychoactive agents, physostigmine is useful for reversal of the central nervous symptoms of the acute intoxication itself. In addition it can be used for prevention of some withdrawal states. In
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PMID:Central anticholinergic syndrome (CAS) in anesthesia and intensive care. 268 49

Acetylcholine (ACh) in low doses (0.1-1 microM) reversibly inhibits voltage-dependent activation of the "pacemaker" current, if, in isolated sino-atrial node cells. This action is brought about by a negatively-directed shift of the current activation curve, opposite to that due to catecholamines on the same current. The if inhibition is antagonized by atropine, indicating the involvement of muscarinic receptors. In cells incubated in pertussis toxin-containing solutions, if does not respond to ACh, suggesting that G-proteins mediate the ACh-induced if depression. Further, ACh can inhibit if following catecholamine-induced stimulation, but has a negligible effect on if stimulated by forskolin, a direct activator of adenylate-cyclase. Our results indicate that ACh acts on if by inhibiting basal adenylate-cyclase activity.
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PMID:Acetylcholine inhibits activation of the cardiac hyperpolarizing-activated current, if. 282 12

Three N-ethyl substituted analogs of acetylcholine (ACh) were evaluated for potential use as false neurotransmitters to decrease cholinergic transmission. This evaluation included (1) the elevation of arterial blood pressure upon central administration, (2) depression of blood pressure upon intravenous injection and (3) interactions with central muscarinic and peripheral nicotinic receptors. With respect to the central pressor response, ACh, acetylmonoethylcholine (AMECh) and acetyldiethylcholine (ADECh) were full agonists of decreasing potency; acetyltriethylcholine (ATECh) was a partial agonist of considerably lower potency. The duration of response paralleled potency. With respect to the peripheral depressor response, ACh and AMECh were full agonists of equal potency, and ADECh and ATECh were partial agonists of at least 100-fold lower potency. In terms of their affinity for central muscarinic receptors (brainstem and cerebral cortex), the following series was obtained: ACh greater than AMECh much greater than ADECh = ATECh. All of the agents had a greater affinity for muscarinic receptors in the brainstem compared to cortex. Acetylcholine and AMECh recognized multiple receptor binding conformations; the binding of ADECh and ATECh indicated interaction with a single set of equivalent sites. The affinity for nicotinic ACh receptors from the Torpedo electric organ was ACh = AMECh much greater than ADECh; ATECh had little affinity for these receptors. Acetylcholine, AMECh and ADECh stimulated the binding of [3H]phencyclidine to the ion channel of nicotinic receptor (potency series = ACh greater than AMECh = ADECh); ATECh was inactive. Acetylcholine, AMECh and ADECh also induced receptor conversion to a desensitized conformation; ATECh did not.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cholinergic false transmitters: physiological and biochemical actions in central and peripheral systems. 283 48

Intracellular and voltage-clamp recordings were made from sympathetic B neurons to investigate an interaction between peptidergic and cholinergic responses in bullfrog sympathetic ganglia. Stimulations of both 3rd-5th (0.2 Hz) and 8th (30 Hz) spinal nerves evoked the fast excitatory postsynaptic potential (EPSP) superimposed with the late slow EPSP at the same sympathetic neuron. The amplitude of fast EPSPs was decreased during the course of the late slow EPSP in a majority of sympathetic neurons. The mean depression of the fast EPSP amplitude was 51 +/- 4% (n = 24). The quantal content of the fast EPSP was also depressed by 54 +/- 3% (n = 10) during the late slow EPSP. Acetylcholine-induced depolarization (ACh potential) and current (ACh current) produced by an ionophoretic application of ACh were not reduced during the late slow EPSP. Bath-application of LH-RH (40 nM-4 microM) depressed the fast EPSP in a concentration-dependent manner; at a concentration of 1 microM, it produced a 63 +/- 8% (n = 8) depression of the quantal content of the fast EPSP. LH-RH (1-4 microM) depressed the frequency of the miniature (M) EPSPs by 25 +/- 4% (n = 5) of control. Antagonists for luteinizing hormone-releasing hormone (LH-RH) receptor, [D-Phe2,6, Pro3]-LH-RH and [D-pGlu1, D-Phe2, D-Trp3,6]-LH-RH, prevented the presynaptic inhibition of the fast EPSP induced by LH-RH. These results suggest that the fast EPSP is depressed during the late slow EPSP by decreasing the evoked release of ACh from presynaptic nerve terminals in bullfrog sympathetic ganglia.
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PMID:Peptidergic inhibition of cholinergic transmission in bullfrog sympathetic ganglia. 285 75

We used the electric organ of Torpedo, a modified neuromuscular system, to investigate the direct effects of antipsychotic drugs on cholinergic transmission. All the antipsychotic drugs tested inhibited transmission by decreasing the amount of ACh released by nerve impulses. Their potency for this action was as follows: trifluoperazine less than clozapine less than thiethylperazine less than droperidol less than haloperidol less than chlorpromazine = beta-flupentixol less than alpha-flupentixol. Depression of ACh release by antipsychotics was poorly reversible, and was not mediated by dopamine receptors in this system since neither dopamine nor apomorphine had any effect on transmission. Antipsychotics did not act through presynaptic cholinergic receptors since the effect was not antagonized by atropine or quinuclidinyl benzilate. Trifluoperazine had no effect on the total ACh content of the tissue, on the compartmentation of ACh inside and outside synaptic vesicles, or on the rate of ACh turnover or the accumulation of 45Ca observed after repetitive stimulation. We conclude that antipsychotic drugs depress the neurally evoked release of ACh by acting directly on the releasing mechanism.
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PMID:Antipsychotic drugs depress acetylcholine release in the Torpedo electric organ, a purely cholinergic system. 286 52

The present study demonstrates that the reversible and irreversible anti-ChE agents have direct actions on the nicotinic acetylcholine receptor-ionic channel (AChR) and on the locust glutamatergic neuromuscular junction. In addition, the prophylaxis of lethality of organophosphorus anti-ChE compounds was studied. The lethality of VX and sarin was diminished when the rats were pretreated with physostigmine and atropine. The effectiveness of this protection, however, was markedly increased when a ganglionic blocker, either mecamylamine or chlorisondamine, was added, such that all the animals survived after receiving four times a lethal dose of VX. Pretreated animals receiving sarin showed significant recovery of morphological and functional properties of the neuromuscular junction as compared to the damage of structures from animals without pretreatment. Blood ChE inhibition was slightly decreased while brain and muscle AChE levels were significantly recovered (from 98 and 70% to 56 and 32%, respectively) by the pretreatment. This effect may partially explain the protection given by physostigmine but not that afforded by addition of a non-anti-ChE agent. Physostigmine, at concentrations greater than 20 microM, showed both a marked depression of the peak amplitudes of the endplate current (EPC) and a shortening of the decay time constants tau EPC. These effects were mostly due to a direct drug interaction with the nicotinic AChR blocking the ionic channel in its open conformation. Single-channel recordings showed that physostigmine decreases conductance and open times of the channels activated in the presence of ACh and in addition has an agonistic property on the nicotinic AChR. VX, on the other hand, only shortened the open times of ACh-activated channels without affecting the conductance. No agonist property was detected with VX. On glutamatergic synapses, the ChE inhibitors generated spontaneous firing of end-plate potentials (EPPs) and action potentials (APs). This effect was blocked in the presence of low external Ca2+ concentration or tetrodotoxin. It seems that the spontaneous EPP and AP firing resulted from an increased transmitter release induced by an increase in Na+ influx at the presynpatic nerve terminal. Physostigmine and some irreversible ChE inhibitors (VX and DFP) also blocked the postjunctional glutamate receptors. Similar to the nicotinic AChR, this effect was mostly related to a blockade of the open channels. In conclusion, the present studies showed significant protection of rats by physostigmine in combination with some ganglionic antagonists against lethality by organophosphate agents.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Multiple actions of anticholinesterase agents on chemosensitive synapses: molecular basis for prophylaxis and treatment of organophosphate poisoning. 286 60

The efficacy of evoked ACh release by intact and newly sprouted terminals in response to partial denervation and expansion of the motor neuron terminal field was studied in mouse soleus muscle after section of the L-5 spinal root. From 2 to 4 d after partial denervation until 90 d later, only 3-7 motor units of the normal 21 remained. Regeneration of the dissected nerve was prevented while the remaining motor units were sprouting. The indirect twitch, which was only 20% of direct twitch tension 2-4 d after nerve section, recovered between 28 and 50 d postoperatively. However, the depression of twitch in low Ca/high Mg solution, which was equal to control 2-3 d postoperatively, was 2-3 times more depressed than control by 50 d and remained so up to 90 d. This indicated persistent reduction of the safety factor in sprouted motor units. Intracellular measurement of quantal content in 0.4 mM Ca, 2.75 mM Mg revealed 2 groups of nerve terminals in partially denervated muscle. The quantal content of the first group was greater than contralateral control at earlier times (28-50 d) and only slightly greater than control later (74 and 90 d). This group consisted of the original undenervated terminals, since it was associated with normal miniature endplate potential (MEPP) frequency and end-plate potential (EPP) latency, and presumably with the class of fibers with normal (zinc iodide osmium-stained) nerve terminal morphology and occasional large myelinated preterminal axons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of partial denervation and terminal field expansion on neuromuscular transmitter release and nerve terminal structure. 289 99

1-Methylisoguanosine, a marine natural product analogue of adenosine, with moderate activity as a benzodiazepine receptor ligand, has previously been shown to have muscle-relaxant and hypothermic activity in mice in vivo. The present experiments showed that the benzodiazepine antagonist Ro15-1788 did not block the in vivo muscle-relaxant and hypothermic effects of 1-methylisoguanosine, suggesting that these particular actions are not due to interactions with benzodiazepine receptors. When applied by microiontophoresis near spontaneously-active neurones or neurones activated by ACh, DL-homocysteate or glutamate in the ventrobasal thalamus of anaesthetized rats, 1-methylisoguanosine had a depressant action; it was similar to adenosine in potency and in its ability to be antagonized by 8-(parasulphophenyl)theophylline. The depression was usually longer lasting than that caused by adenosine, consistent with previous neurochemical data showing it to be resistant to adenosine deaminase and a poor substrate for the uptake system for adenosine in the CNS. These results suggest that the major pharmacological/behavioural actions of 1-methylisoguanosine in vivo are more likely to be caused by an interaction with adenosine receptors, rather than with benzodiazepine sites.
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PMID:1-Methylisoguanosine: interaction with central adenosine receptors and lack of antagonism of its in vivo effects by a benzodiazepine antagonist. 303 18

Acetylcholine causes pulmonary vasodilation, but its mechanism of action is unclear. We hypothesized that acetylcholine-induced pulmonary vasodilation might be associated with prostacyclin formation. Therefore, we used isolated rat lungs perfused with a recirculating cell- and plasma-free physiological salt solution to study the effect of acetylcholine infusion on pulmonary perfusion pressure, vascular responsiveness and lung prostacyclin production. Acetylcholine (20 micrograms infused over 1 minute) caused immediate vasodilation during ongoing hypoxic vasoconstriction and prolonged depression of subsequent hypoxic and angiotensin II-induced vasoconstrictions. Both effects of acetylcholine were abolished by atropine pretreatment. The prolonged acetylcholine effect, but not the immediate response, was blocked by meclofenamate, an inhibitor of cyclooxygenase. The prolonged effect, but not the immediate response, of acetylcholine was associated with an increase in perfusate 6-keto-PGF1 alpha concentration. The acetylcholine stimulated increase in 6-keto-PGF1 alpha production was inhibited by meclofenamate and by atropine. Thus, blockade of prostacyclin production corresponded with blockade of the prolonged acetylcholine effect. In conclusion, acetylcholine caused in isolated rat lungs an immediate vasodilation and a prolonged, time-dependent depression of vascular responsiveness. Whereas both acetylcholine effects were under muscarinic receptor control, only the prolonged effect depended on the cyclooxygenase pathway and, presumably, prostacyclin synthesis.
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PMID:Acetylcholine induces vasodilation and prostacyclin synthesis in rat lungs. 308 79

Acetylcholine (20 to 100 micrograms) was infused directly into coronary arteries in 10 patients with variant angina (group A), 13 subjects without coronary artery disease (group B) and 8 patients with significant organic coronary artery stenosis (greater than or equal to 50%) but without variant angina (group C) during coronary arteriography, to clarify the action of this agent on coronary arteries. Temporary pacing was performed at a demand heart rate of 40 beats/min while bradyarrhythmia developed. Coronary arteriography after administration of acetylcholine showed coronary vasoconstriction in all 10 patients (100%) of group A. Angina accompanied by electrocardiographic ischemic changes in 9 of 10 (90%, 7 ST-segment elevation and 2 depression) was provoked during this test. In the patients of group B, acetylcholine also induced vasoconstriction in 8 of 22 (36%) coronary arterial systems examined, chest pain in 3 (14%) and ST-segment deviation in none (0%). In the patients of group C, acetylcholine induced vasoconstriction in 3 of 9 (33%), chest pain in 2 (22%) and ST-segment depression in 1 (11%). No definite coronary artery dilation induced by acetylcholine was noted. Coronary vasoconstriction (p less than 0.05), electrocardiographic ischemic findings (p less than 0.01) and chest pain (p less than 0.01) were induced significantly more frequently in group A than in both groups B and group C. No significant difference was found between group B and group C. The coronary arteries in the patients with variant angina seem to be more susceptible to acetylcholine than those of patients without variant angina irrespective of the presence of significant atherosclerosis.
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PMID:Supersensitivity of coronary arteries in variant angina to spasm induced by intracoronary acetylcholine. 333 20

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