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 influence of choline- and serotoninergic agents on the pedal self-stimulation (SS) was studied in male rats of Wistar line. Physostigmine decreased the frequency of pressing on the pedal whereas fluoxetine didn't influence SS. Scopolamine activated SS and lowered the threshold of the SS-reaction. P-chloroamphetamine effect depended on the action phase of the drug and was manifested both in depression and activation of SS. Preliminary administration of fluoxetine decreased the activating effect of scopolamine and enhanced the depressing effect of physostigmine. A combination of p-chloroamphetamine and cholinergic agents was accompanied by a tendency toward weakening of depressing effect of physostigmine and toward enhancing of activating effect of scopolamine. It is suggested that serotoninergic mechanisms in case of changes in activity of cholinergic processes, depress the system of positive reinforcement. A functional interaction of choline- and serotoninergic neurotransmitter systems seems probable.
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PMID:[Effect of cholin- and serotoninergic substances on self stimulation in rats]. 22 89

The role of cholinergic neurons in the motor depressant effects of ethanol was examined. Choline chloride pretreatment (30-90 mg/kg i.p.) potentiated the hypomotility produced by 2 g/kg of ethanol. Physostigmine pretreatment (0.2 mg/kg i.p.) also enhanced the motor depression produced by ethanol. Conversely, in animals pretreated with scopolamine (0.25 and 0.5 mg/kg) the depressant effect of ethanol was less. The potentiation produced by choline was not associated with changes in levels of ethanol in blood. It is concluded that cholinergic neurons are involved in the motor activity changes produced by ethanol. Such a mechanism may operate in conjunction with the dopaminergic neuronal system.
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PMID:Cholinergic mediation of motor effects of ethanol in rats. 43 43

Physostigmine in a dose of 0.1 mg/kg i.v. expressly stimulated the oxygen uptake in the rat cerebral cortex. This effect was blocked by propranolol and seems be mediated by catecholamines. Since atropine also antagonized the stimulant effect of physostigmine, it appears that the action of physostigmine is primarily cholinergic and that the adrenergic effect is a secondary phenomenon. The higher dose of physostigmine (0.4 mg/kg i.v.) caused a depression of rat brain oxygen uptake.
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PMID:The effects of physostigmine on the oxygen uptake in rat brain tissue. 44 22

Involvement of the cholinergic and catecholaminergic mechanisms in the caudate spindle recorded from the anterior and posterior sigmoid gyri was examined in cats. Physostigmine (0.01 to 0.1 mg/kg i.v.) abolished the appearance of the caudate spindle. These inhibitory effects were antagonized by the administration of atropine (0.25 to 1 mg/kg i.v.). The caudate spindle was inhibited by high frequency stimulation of the mesencephalic reticular formation: This inhibitory effect was antagonized by atropine. On the other hand, L-DOPA (25 to 50 mg/kg, i.v.), L-DOPA + MAO inhibitor and methamphetamine (0.5 to 5 mg/kg i.v.) did not influence the caudate spindle. These results suggest an involvement of cholinergic mechanism in depression of the caudate spindle.
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PMID:Involvement of the cholinergic mechanism in depression of the caudate spindle. 53 59

To investigate the effect of physostigmine on central nervous system (CNS) depression produced by halothane, control halothan minimum alveolar concentration (MAC) measured over 1 hour in 7 dogs was compared to MAC 30 minutes after each sequential IV dose of 0.04, 0.4, and 4 mg/kg physostigmine. MAC decreased 6.8, 11.1 (p less than 0.05), and 35.9 (p less than 0.01) percent, respectively. Six dogs were observed for an acute increase in halothane requirement in the first 30 minutes after administration of physostigmine. All 6 showed such a response at 1 or more dose levels, beginning within 1 to 5 minutes after administration and lasting 2 to 30 minutes (p less than 0.05). Five other dogs were tested with neostigmine in the same doses and showed respective decreases in MAC of 7.9, 16.6 (p less than 0.01), and 17.5 ( less than 0.01) percent. No dog showed an acute increase in anesthetic requirement. Intravenous atropine 0.5 mg/kg failed to further alter MAC after 4 mg/kg neostigmine. Physostigmine transiently antagonizes halothane anesthesia, presumably by facilitating cholinergic transmission in the CNS; neostigmine does not. After this initial response, both drugs decrease anesthetic requirement. If these data may be extrapolated to patients, they suggest that physostigmine is not an effective antagonist to postoperative somnolence due to halothane.
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PMID:Physostigmine and anesthetic requirement for halothane in dogs. 56 55

1. Cholinomimetic and adrenomimetic substances were tested on the chemosensitive zones of the ventral surface of the medulla oblongata using a plexiglas ring method. Tidal volume and respiratory frequency, arterial pressure and heart frequency were observed. 2. The increase of ventilation and the depression of arterial blood pressure by locally applied acetylcholine could be blocked by previous local application of atropine. It is therefore assumed that the acetylcholine receptors have muscarinic properties. 3. Nicotine in a small dose raises arterial pressure and with higher doses a drop is observed. The responses of respiration and of arterial pressure to nicotine were blocked by previous intravenous administration of hexamethonium. 4. Local application of atropine in the caudal (L) and rostral (M) chemosensitive zones reduced resting ventilation and the slope of the ventilatory response to CO2-inhalation. Physostigmine in these areas enhanced resting ventilation leaving unchanged the slope of the ventilatory response to CO2-inhalation. 5. With high concentrations of (L)-noradrenaline and (L)-adrenaline a slight increase of arterial pressure was seen while serotonin caused a drop. 6. These results together with those of Fukuda and Loeschcke (1978) suggest that a cholinergic transmission in the surface layer of the ventral medulla is a component in the respiratory and circulatory control systems.
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PMID:A cholinergic mechanism involved in the respiratory chemosensitivity of the medulla oblongata in the cat. 57 Nov 2

The carotid body and its own nerve were removed from cats anesthetized with sodium pentobarbital and placed in an air gap system; the carotid body was bathed in modified Locke's solution equilibrated with 50% O2 in N2, pH 7.43 at 35 degrees C. The sensory discharges, changes in "resting" receptor polarization and the mass receptor potential evoked by ACh or NaCN were recorded with nonpolarizable electrodes placed across the gap. Receptor potentials and sensory discharges evoked by ACh showed an appreciable increase in amplitude and frequency when the preparation was bathed in eserinized Locke. Eserine did not change appreciably the responses evoked by NaCN. Excessive depolarization elicited by either ACh or NaCN was accompanied by sensory discharge block. Removal of K+ ions from the bathing solution induced receptor hyperpolarization and an increase in the amplitude of the evoked receptor potentials. An increase of K+ concentration had the opposite effect. Reduction of Na+ or NaCl to one half, or total removal of this salt, induced an initial reduction and later disappearance of the sensory discharges, some receptor hyperpolarization and a reduction in the amplitude of the evoked receptor potential. Reduction or removal of Ca++ produced receptor depolarization, a marked depression of the evoked receptor potentials, an increase in the frequency of the sensory discharges and a reduction in the amplitude of the nerve action potentials. High Ca++ or Mg++ had little or no effect on action potential amplitude or resting polarization, but decreased sensory discharge frequency and the evoked receptor potentials. Total or partial replacement of Ca++ with Mg++ induced complex effects: (1) receptor depolarization which occurred in low Ca++, was prevented by addition of Mg++ ions; (2) the amplitude of the evoked receptor potentials was depressed; (3) the nerve discharge frequency was reduced as it was in high Mg++ solutions; and (4) the amplitude of the nerve action potentials was reduced as it was in low Ca++ solutions. Temperature had a marked effect on the chemoreceptors since at high temperatures the receptors were depolarized and the discharge frequency increased. The baseline discharge and responses evoked by ACh or NaCN were depressed at low temperatures. The results are discussed in terms of possible receptor mechanisms influenced by the different ions.
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PMID:Effects of different ions on resting polarization and on the mass receptor potential of carotid body chemosensors. 97 3

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

There are at least five mechanisms by which the central nervous system regulates neural and humoral systems that control the blood pressure (BP). Particular attention has been paid to central cholinergic-adrenergic interactions in the regulation of BP. Physostigmine and other anticholinesterases which penetrate the blood-brain barrier, both carbamates and organophosphates, produce an increase of BP. This effect can be abolished by atropine, but not by methylatropine. The available evidence indicates that physostigmine and other AChE inhibitors initially produce an activation of central muscarinic receptors, which subsequently leads to an increase of the peripheral adrenergic activity. The hypertensive response to physostigmine is possible only if a functionally competent ChE is present in the brain. This effect of physostigmine is regularly associated with a dose-related increase in the neural activity in the preganglionic fibers of the cervical sympathetic nerve. BP rise after physostigmine is significantly less in immunosympathectomized animals and almost completely abolished after chemical sympathectomy. Physostigmine significantly increased the plasma concentration of catecholamines. After electrocoagulation of the locus coeruleus, not only did a significant decrease occur in the basic level of noradrenaline in plasma, but there was also a strong depression of the noradrenaline plasma response to physostigmine and immobilization. Physostigmine increased lipolysis and glycogenolysis, whereas neostigmine did not produce any change. Several directly acting cholinergic agonists alter the functions of the cardiovascular system when injected directly into the cerebral ventricular system, or directly into various brain regions. The most probable sites of action of AChE inhibitors and directly acting cholinergic agonists are the locus coeruleus, the nucleus tractus solitarii and the rostral ventrolateral medulla (RVLM). The primary activation of the cholinergic synapse is believed to take place in RVLM. Met-enkephalin, Leu-enkephalin and beta-endorphin, when applied exogenously, depress or even abolish the hypertensive effect of physostigmine. The same type of response was obtained after application of substances which inhibit the enkephalin-degrading enzymes (bestatin, phosphoramidon). Thus, the exogenous or endogenous enkephalins activate the opioid receptors in the brain and at the same time produce a depression of the cholinergic-adrenergic interaction in the central nervous system, which is a prerequisite for the hypertensive response to physostigmine. The functional role of the central cholinergic mechanisms in BP control under physiological conditions has not been established with certainty. These mechanisms might have a more significant role under pathological or homeostatic disturbances. For example, physostigmine showed a life-saving effect in acute hypovolemic shock in rabbits.
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PMID:Transmitter interactions in the central cholinergic control of blood pressure regulation. 168 40

This study compared the effects of 3 novel antiAChE agents (derivatives of dimethylaminoethyl-phenyl carbamate) with that of physostigmine on the respiratory depression induced by morphine in rabbits. Each drug, RA6, (1 mg i.v., 2 mg s.c.) RA7 (1 or 2 mg i.v.); RA15 (0.25 or 0.5 mg i.v.), physostigmine (0.05 or 0.1 mg i.v.) or saline (1 ml), was injected simultaneously with morphine (8 mg i.v.) to groups of 6-10 rabbits. Respiration rate, blood gases and pH were monitored for 3 hr. Plasma ChE was measured before and at 15 min intervals after injection. The 4 antiAChE's were given to 40 other rabbits, which were sacrificed at the time of maximal antagonism of the respiratory depressant effect of morphine, in order to measure the activity of AChE in the medulla, cortex and hippocampus. Physostigmine (0.1 mg) only antagonized the increase in paCO2 induced by morphine at 15 and 30 min. The drugs RA15 (0.5 mg), RA6 (2.5 mg) and RA7 (2 mg) almost completely prevented the respiratory depression, without obvious signs of peripheral cholinergic hyperactivity, for at least 3 hr. There was no relationship between the degree of antagonism of the effects of morphine with any drug and that of inhibition of ChE in plasma. In contrast, a highly significant correlation (P less than 0.01) was found between the former and the amount of inhibition of AChE in the medulla. It is suggested that the novel carbamates may have potential therapeutic application in reducing the respiratory depression of opiates, without impairing analgesia.
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PMID:Antagonism of morphine-induced respiratory depression by novel anticholinesterase agents. 175 86


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