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)

1. The effects of muscarinic antagonists on cationic current evoked by activating muscarinic receptors with the stable agonist carbachol were studied by use of patch-clamp recording techniques in guinea-pig single ileal smooth muscle cells. 2. Ascending concentrations of carbachol (3-300 microM) activated the cationic conductance in a concentration-dependent manner with conductance at a maximally effective carbachol concentration (Gmax) of 27.4+/-1.4 nS and a mean -log EC50 of 5.12+/-0.03 (mean+/-s.e.mean) (n=114). 3. Muscarinic antagonists with higher affinity for the M2 receptor, methoctramine, himbacine and tripitramine, produced a parallel shift of the carbachol concentration-effect curve to the right in a concentration-dependent manner with pA2 values of 8.1, 8.0 and 9.1, respectively. 4. All M3 selective muscarinic antagonists tested, 4-DAMP, p-F-HHSiD and zamifenacin, reduced the maximal response in a concentration-dependent and non-competitive manner. This effect could be observed even at concentrations which did not produce any increase in the EC50 for carbachol. At higher concentrations M3 antagonists shifted the agonist curve to the right, increasing the EC50, and depressed the maximum conductance response. Atropine, a non-selective antagonist, produced both reduction in Gmax (M3 effect) and significant increase in the EC50 (M2 effect) in the same concentration range. 5. The depression of the conductance by 4-DAMP, zamifenacin and atropine could not be explained by channel block as cationic current evoked by adding GTPgammaS to the pipette (without application of carbachol) was unaffected. 6. The results support the hypothesis that carbachol activates M2 muscarinic receptors so initiating the opening of cationic channels which cause depolarization; this effect is potentiated by an unknown mechanism when carbachol activates M3 receptors. As an increasing fraction of M3 receptors are blocked by an antagonist, the effects on cationic current of an increasing proportion of activated M2 receptors are disabled.
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PMID:Muscarinic receptor subtypes controlling the cationic current in guinea-pig ileal smooth muscle. 938 4

1. The effect of crude honeybee (Apis mellifera) venom on the skeletal, smooth as well as cardiac muscles were studied in this investigation. 2. Perfusion of gastrocnemius-sciatic nerve preparation of frogs with 1 microgram/ml venom solution has weakened the mechanical contraction of the muscle without recovery. Blocking of nicotinic receptors with 3 micrograms/ml flaxedil before bee venom application sustained normal contraction of gastrocnemius muscle. 3. The electrical activity of duodenum rabbits was recorded before and after the application of 1 microgram/ml venom solution. The venom has depressed the amplitude of the muscle contraction after 15 min pretreatment with atropine nearly abolished the depressor effect of the venom on smooth muscle. 4. In concentrations from 0.5-2 micrograms/ml, bee venom caused decrease of heart rate of isolated perfused toad heart. This bradycardia was accompanied by elongation in the P-R interval. A gradual and progressive increase in the R-wave amplitude reflected a positive inotropism of the venom. Application of 5 micrograms/ml verapamil, a calcium channels blocking agent, abolished the noticed effect of the venom. 5. Marked electrocardiographic changes were produced within minutes of the venom application on the isolated perfused hearts, like marked injury current (elevation or depression of the S-T segment), atrioventricular conduction disturbances and sinus arrhythmias. Atropine and nicotine could decrease the toxic effect of the venom on the myocardium. 6. Results of the present work lead to the suggestion that bee venom is mediated through the peripheral cholinergic neurotransmitter system. General neurotoxicity of an inhibitory nature involving the autonomic as well as neuromuscular system are established as a result of the venom, meanwhile a direct effect on the myocardium membrane stabilization has been suggested.
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PMID:Mechanism of action of honey bee (Apis mellifera L.) venom on different types of muscles. 958 89

Psychoses caused by an intoxication with atropine or scopolamine are rarely published. Nevertheless atropine and scopolamine were being used in the ancient civilisations and are still in use today. The intoxication is characterised by dose-dependent and substance-dependent syndrome with specific central and peripheral symptoms. Atropine and scopolamine cause a central and peripheral anticholinergic blockade of the muscarine receptor. Psychiatric symptoms include restlessness, excitement, hallucinations, euphoria, disorientation but also stupor, coma and respiratory depression. History, pathophysiology and clinical symptoms of the intoxication due to the alkaloids of the solanaceae are presented. A review of literature is given and four own cases observed in one year are introduced.
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PMID:[Toxic psychoses from atropine and scopolamine]. 969 3

We investigated the contribution of perivascular nerves and neurotransmitters to cortical spreading depression (CSD)-associated hyperperfusion in the rat. Chronic transection of the nasociliary nerve (NCN, 2 wk before) decreased ipsilateral CSD-associated hyperperfusion by 23 +/- 13% (mean +/- SD; n = 5, P < 0.05), whereas acute transection of the NCN or sham surgery had no effect (n = 8). When the NCN and parasympathetic nerve fibers (PSN) were both chronically transected, CSD hyperperfusion was attenuated by 55 +/- 19% (n = 5, P < 0.05). Cerebrovascular reactivity to hypercapnia was not significantly affected. Brain topical superfusion of the muscarinic receptor antagonist atropine (10(-4) M) caused a reduction of CSD hyperperfusion by 41 +/- 13% (n = 5, P < 0.05). The competitive blockade of calcitonin gene-related peptide (CGRP) receptors by CGRP-(8-37) (5 x 10(-7) M) afforded a decrease by 49 +/- 19% (n = 5, P < 0.05), without affecting CO2 reactivity (n = 4). The combined application of both CGRP-(8-37) and atropine further attenuated CSD hyperperfusion (by 69 +/- 17%, n = 5, P < 0.05). After chronic NCN and PSN transection brain topical superfusion of CGRP-(8-37) (5 x 10(-7) M) reduced CSD hyperperfusion slightly by 9.5 +/- 5% (n = 3). Atropine (10(-4) M) afforded a decrease by 17 +/- 6% (n = 3). These reductions were not statistically significant. We conclude that CSD-associated hyperperfusion is mediated in part by a depolarization of trigeminal sensory and parasympathetic nerve fibers, resulting in a release of vasoactive trigeminal and parasympathetic neurotransmitters.
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PMID:Perivascular nerves contribute to cortical spreading depression-associated hyperemia in rats. 984 81

The aim of the present study was to investigate whether the activation of muscarinic receptors is a preliminary step to the endogenous release of nitric oxide modulating nicotinic transmission within the prevertebral ganglia. This work has been performed in vitro in isolated rabbit coeliac ganglion. The electrical activity of the ganglionic neurons was recorded using intracellular recording techniques. When a train of pulses of supramaximal intensity was applied to the splanchnic nerves, gradual depression of fast nicotinic transmission occurred: the pulses do not systematically elicit action potentials, but very often elicit excitatory postsynaptic potentials only. The use of pharmacological agents that interfere with the nitric oxide pathway such as L-arginine (precursor of nitric oxide) or 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (nitric oxide scavenger) demonstrated that nitric oxide modulates this depression phenomenon by facilitating or inhibiting the nicotinic transmission of the ganglionic neurons. A nitric oxide donor (diethylamine/nitric oxide complex) induced an inhibition of the nicotinic synaptic transmission. In the presence of the muscarinic receptors antagonist atropine, L-arginine and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide failed to modify the nicotinic transmission of the ganglionic neurons but diethylamine/nitric oxide complex was still able to inhibit it. These results demonstrate that in the coeliac ganglion, the activation of muscarinic cholinergic receptors is a prerequisite for the activation of neuronal nitric oxide synthase in preganglionic fibres. The nitric oxide released then exerts a facilitation or an inhibition of the nicotinic transmission of the ganglionic neurons. Atropine triggered a facilitation of the nicotinic transmission when superfused alone and an inhibition when superfused in the presence of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide. These results confirm that muscarinic receptors activate the nitric oxide pathway modulating the nicotinic transmission of the prevertebral neurons. Our results also demonstrate that when the nitric oxide pathway is blocked, activation of muscarinic receptors leads to facilitation of the nicotinic transmission. Our study brings new insights concerning the modulation by nitric oxide and by muscarinic receptors of the synaptic transmission within the prevertebral ganglia.
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PMID:Muscarinic receptor activation is a prerequisite for the endogenous release of nitric oxide modulating nicotinic transmission within the coeliac ganglion in the rabbit. 1068 20

Atropine has previously been found to suppress visually induced myopia both in animals and humans. The mechanism of its action is unclear. We have studied its retinal effects in an in vitro preparation, using the retina-pigment epithelium-choroid complex of the chick eye. In vivo, deprivation myopia was induced by translucent goggles. Atropine solution was injected into the vitreous at two-day intervals. Dopamine release from the retina following atropine injection in vivo and from the in vitro retina preparation was quantified by HPLC-EC. In vitro preparations of the isolated chick retina-pigment epithelium-choroid were superfused with atropine. Light-induced potentials (local ERG), slow standing potentials from the retinal pigment epithelium/neural retina, and extracellular potassium concentrations were recorded. In line with previous findings, intravitreal injections of atropine (25 microg, 250 microg) reduced deprivation myopia in a dose-dependent manner. Atropine increased the release of the neurotransmitter dopamine into the superfusate in vitro at 100-500 microM and into the vitreous in vivo at 250 microg. Before an increase was measured in the vitreous, the retinal dopamine content was elevated. In concentrations equivalent to the intravitreal concentration to suppress myopia in vivo (200-800 microM), atropine induced spreading depression (SD) in the in vitro preparation. In contrast, muscarinic agonists, acetylcholine and pilocarpine, did not induce SD. Atropine reduced the ERG b- and d-wave, led to damped oscillations of RPE potentials, and reversed the ERG c-wave. Atropine suppressed myopia only at doses at which severe nonspecific side effects were observed in the retina. Atropine seems to intrude massively into the vital functions of the retina as indicated by the occurrence of SD. We conclude that atropine, by inducing SD, boosts neurotransmitter release from cellular stores, which may cancel out a presumed retinal signal that controls eye growth and through this, myopia.
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PMID:Effects of atropine on refractive development, dopamine release, and slow retinal potentials in the chick. 1082 71

A method has been described for the study of the central effects produced by the intracerebral injection of drugs in the unanaesthetized mouse. The effects observed were in good agreement with those obtained after similar injections in cats, dogs and human beings. After intracerebral injection, drugs of diverse structure produced certain generalized effects: changes in positioning of the tail, stupor, hyperexcitability and tachypnoea. Both acetylcholine and methacholine produced an akinetic seizure and depression, but the latter compound also caused lacrimation and salivation. Atropine produced piloerection, increased sensitivity to sound and touch, clonic convulsions and scratching, whereas hexamethonium caused Parkinsonian-like muscle tremors and peripheral vasodilatation. After adrenaline, hyperexcitability, exophthalmos, stupor and death from pulmonary oedema were observed, but (+)-methylamphetamine produced only piloerection and exaggerated activity in response to sound and touch. Ergotamine caused a decreased sensitivity to sound and touch, micturition, and stupor, while ergometrine caused clonic convulsions, piloerection, defaecation and stupor.
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PMID:Pharmacological effects produced by intracerebral injection of drugs in the conscious mouse. 1341 44

Veratridine hydrochloride injected subcutaneously into unanaesthetized rats inhibited water diuresis. A linear relationship between log dose and antidiuretic effect could be established over the dose range 50 to 200 mug./100 g. of body weight. When veratridine hydrochloride was injected intravenously in doses from 10 to 30 mug./100 g., this relationship was also linear. In terms of its antidiuretic action, the alkaloid was approximately five times as effective when given intravenously. Rats anaesthetized with urethane responded to an intravenous injection with a more pronounced inhibition than unanaesthetized animals. Protoveratrine injected intravenously into unanaesthetized rats showed no clear relationship between dose and magnitude of antidiuretic effect. Veratridine hydrochloride injected intravenously had a pronounced hypotensive effect in both anaesthetized and unanaesthetized rats. Treatment with atropine did not affect this hypotensive action significantly. Atropine given subcutaneously 30 min. before an intravenous injection of veratridine hydrochloride abolished or diminished the inhibitory effect of veratridine on water diuresis. Veratridine hydrochloride injected intravenously into unanaesthetized rats caused a marked depression of the clearance of inulin and p-aminohippurate. In unanaesthetized rats with an osmotic diuresis, veratridine hydrochloride produced its usual antidiuretic effect. The urine of rats injected with veratridine hydrochloride produced an antidiuretic effect when injected intravenously into other animals. The antidiuretic potency of such urines was not affected by treatment with thioglycollate. Animals injected with veratridine excreted small amounts of a veratridine-like substance in the urine. These results do not suggest that veratridine in antidiuretic and hypotensive doses stimulated the neurohypophysis in the rat.
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PMID:Renal effects of veratridine. 1365 82

By comparing the effects on ganglionic transmission and on the pre- and post-ganglionic nerves in the isolated superior cervical ganglion preparation of the rat, the selectivity of several drugs was assessed quantitatively. Hexamethonium, tetraethylammonium, nicotine and tubocurarine blocked transmission in concentrations which did not affect nervous conduction and were considered to be highly selective in action. Atropine, amylobarbitone and paraldehyde depressed nervous conduction appreciably in ganglion-blocking doses, but not enough to account wholly for the block in transmission and they were therefore considered as being moderately selective. The ganglion blocking actions of mephenesin, procaine, methylpentynol, methylpentynol carbamate and benactyzine were nonspecific, showing general depression of neuronal activity. Ganglion block with bretylium was nonselective in its site of depression of the postganglionic neurone in concentrations which only partly depressed the preganglionic nerve.
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PMID:THE SELECTIVITY OF DRUGS BLOCKING GANGLIONIC TRANSMISSION IN THE RAT. 1422 29

Forty three children ranged from 1 yr. to 6 yr. were randomly assigned to non-atropinized group (n = 20; A(-)) and atropinized group (0.015 mg.kg(-1) i.m., n = 23; A(+)). Control hemodynamics were measured under 0.5% halothane and 67% nitrous oxide and 33% oxygen for three minutes, and then halothane was increased to 2.5% and maintained for 15 min. In the A(-) group, stroke volume (SV) decreased to 64%, heart rate (HR) increased from 100/min to 111/min, and blood pressure (BP) decreased from 65 mmHg to 62 mmHg. Skin blood flow (SBF) concomitantly measured by a laser doppler flowmeter decreased to 48% and total peripheral resistance (TPR) increased to 128%. In the A(+) group, HR increased from 117/min to 132/min ( P < 0.05, vs. A(-) group), BP decreased from 67 mmHg to 66 mmHg. SV decreased to 71% ( P < 0.05, vs. A(-) group). Changes in SBF and TPR were 68% and 128% respectively. End-expired halothane concentration in the A(+) group increased slower than in the A(-) group but not significantly. The results indicate increased sympathetic tone would work as a compensating mechanism for decreased SV and CO. Atropine premedication attenuated cardiovascular depression by maintaining HR and possibly by delaying induction speed of anesthesia. In conclusion, halotane-nitrous oxide anesthesia decreased SV without a marked decrease in heart rate and blood pressure in children. This decrease in SV and BP was attenuated by atropine premedication.
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PMID:Hemodynamic responses during induction of anesthesia with halothane-nitrous oxide in children with or without atropine premedication. 1527 85


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