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

Yohimbine injected intravenously or intracerebroventricularly in conscious dogs produced behavioural excitation accompanied by a rise in blood pressure and heart rate. The cardiovascular effects were reduced or abolished by hexamethonium, phenoxybenzamine and reserpine. In conscious cats intravenously administered yohimbine was depressor but intracerebroventricular administration in these animals caused a rise in blood pressure accompanied by behavioural depression. In anaesthetized or decerebrate cats yohimbine was always depressor. Yohimbine injected intracerebroventricularly produced a rise in blood pressure and heart rate in both conscious and anaesthetized rats. When administered intravenously to these animals there was a fall in blood pressure. It was concluded that the pressor action of yohimbine in conscious dogs was central in origin via the sympathetic nervous system. The different pattern of cardiovascular responses in the dog, cat and rat may be related to differences in the balance between medullary effects and effects on higher brain centres of the three species.
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PMID:The role of the central nervous system in the cardiovascular responses to yohimbine. 24 88

The presence of the endothelium reduced the sensitivity of isolated rabbit carotid artery to endogenous norepinephrine released by electrical stimulation of adrenergic nerves or displaced by tyramine and to exogenously applied norepinephrine, phenylephrine and UK 14304. The maximal contractions induced by the selective alpha 2-agonist UK 14304 were much more profoundly depressed in arteries with endothelium than those induced by the nonselective alpha-adrenoceptor agonist norepinephrine or by the selective alpha 1-agonist. LY 83583, a cyclic-guanosine-monophosphate (GMP)-lowering agent, abolished the endothelium-dependent depression of tone induced by the agonists and converted the sensitivity of arteries with endothelium to that of endothelium-denuded preparations. M & B 22948, a selective cyclic GMP phosphodiesterase inhibitor, significantly inhibited contractions caused by electrical stimulation of adrenergic nerves, tyramine, norepinephrine and UK 14304 in rings with, but not in those without, endothelium. Yohimbine, an alpha 2-adrenoceptor antagonist, increased contractions caused by UK 14304 in rings with endothelium only, but had no significant effect on the contractions caused by exogenously applied norepinephrine or phenylephrine. In the presence of prazosin, an alpha 1-blocker, UK 14304 caused minimal relaxation (about 20%) in rings with endothelium only which were inhibited by yohimbine, suggesting a minor role of direct endothelial cell alpha 2-mediated release of relaxing factors. The over-flow of endogenous norepinephrine caused by electrical stimulation was not affected by treatment with LY 83583 or M & B 22948, suggesting that altering cyclic GMP levels has no major role in prejunctional modulation of norepinephrine release. These findings support the notion that intrinsic levels of cyclic GMP may act as a regulator of adrenergic neurotransmission due primarily to endothelium-derived relaxing factor which is released basally, and to a lesser extent by an activation of endothelial cell alpha 2-adrenoceptors.
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PMID:Cyclic GMP modulators on vascular adrenergic neurotransmission. 135 32

Clonidine as a partial agonist of alpha adrenoceptor in Wistar rat aorta has been documented. It was however observed that the effect of clonidine on the isolated rat aorta of Sprague Dawley rats was slightly different. The concentration effect curve induced by clonidine was on the right of that induced by phenylephrine, with EC50 of 1.5 x 10(-7) M and 3.5 x 10(-4) M for the phenylephrine- and clonidine-induced responses, respectively; but the maximal contraction induced by clonidine was similar to that of phenylephrine. In the presence of clonidine, the concentration effect curve of phenylephrine was shifted to the right. Both the phenylephrine- and clonidine-induced contraction were inhibited by prazosin, and the EC50 values for prazosin in phenylephrine- and clonidine-induced contraction were 1.0 x 10(-8) M and 1.8 x 10(-6) M, respectively. Yohimbine in concentration sufficient to antagonize almost completely the effect of phenylephrine was found to slightly prevent the effects of clonidine. Further increase of clonidine above 2 x 10(-3) M, the concentration sufficient to induce the maximal contraction, however induced depression of the clonidine-induced contraction, and this phenomenon was concentration dependent. Possible explanation of this phenomenon was discussed.
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PMID:Biphasic response of clonidine in isolated rat aortae. 135 56

Quinine, a cinchona alkaloid, was investigated for putative anxiogenic activity in view of clinical reports suggesting that it induces anxiety and apprehension following its use in malaria. The experimental paradigms chosen to elucidate anxiogenic activity have been shown to stand the tests of reliability and validity. Yohimbine, which has been shown to induce anxiety both in animals and in man, was used for comparison. Quinine was found to elicit a complex behavioural profile of activity ranging from overt central stimulation to marked central depression on dose increment. The doses 10 and 20 mg/kg, ip, of quinine chosen to investigate anxiogenic activity were comparable to those induced by 2.5 and 5 mg/kg ip of yohimbine. Quinine induced a dose-related anxiogenic activity in the open-field and elevated plus-maze tests in mice, and the social interaction and thirst conflict tests in rats, similar to effects induced by yohimbine. In addition, both quinine and yohimbine attenuated the effects of diazepam, an anxiolytic agent, in the open-field and thirst conflict tests. The results indicate that quinine exerts significant anxiogenic effect at a particular dose range.
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PMID:Anxiogenic activity of quinine--an experimental study in rodents. 150 13

Systemic administration of yohimbine augments sympathetic outflow and blocks presynaptic alpha 2-adrenergic receptors, releasing the sympathetic neurotransmitter norepinephrine (NE) into the bloodstream. The present study examined sympathoadrenal and hemodynamic responses to yohimbine in 19 patients with essential hypertension and 19 normotensive control subjects. Baseline mean values for arterial NE, epinephrine, dihydroxyphenylglycol (the main intraneuronal metabolite of NE), spillover of NE into arterial plasma, and corticotropin did not differ between the hypertensive and normotensive groups. Yohimbine (0.125 mg/kg i.v. bolus followed by 0.001 mg/kg/min infusion for a total of 15 minutes) increased mean arterial pressure in all but one subject (by 13 +/- 2% [SEM] in the normotensive and 17 +/- 2% in the hypertensive group) and increased arterial NE levels in all subjects (by 253 +/- 50 pg/ml in the normotensive and 312 +/- 51 pg/ml in the hypertensive group). Among hypertensive patients, pressor, cardiac, output, and arterial NE responses were distributed bimodally. Patients with large hemodynamic and NE responses to yohimbine typically reported a history of anxiety, depression, or other psychopathology and of marked pressor or tachycardic episodes during emotional stress. In the hypertensive and normotensive groups, baseline arterial NE concentrations predicted the magnitude of pressor responses to yohimbine (r = 0.59, r = 0.54,p less than 0.01), whereas baseline mean arterial pressure was unrelated to the pressor response. A yohimbine challenge test can identify patients with pressor hyperresponsiveness and can distinguish patients with pressor hyperresponsiveness due to excessive sympathoadrenal reactivity from patients with enhanced postsynaptic responsiveness to endogenous NE.
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PMID:Sympathetic reactivity during a yohimbine challenge test in essential hypertension. 165 75

The present study was undertaken to elucidate the possible actions of yohimbine on cardiac function and metabolism in the hypoxic and subsequently reoxygenated myocardium. For this purpose, rabbit hearts were perfused for 20 min under hypoxic conditions, followed by 45 min reoxygenated perfusion, and their functional and metabolic alterations with and without yohimbine treatment were examined. Hypoxia induced cessation of cardiac contractile force, rise in resting tension and depletion of tissue high-energy phosphates, which were poorly recovered by subsequent reoxygenation. Hypoxia also induced release of creatine kinase and ATP metabolites from perfused hearts and increases in tissue calcium and sodium contents, which were further enhanced upon subsequent reoxygenation. When hypoxic hearts were treated with 3 to 30 microM yohimbine, several beneficial effects were observed in a concentration-dependent manner. This included enhancement of posthypoxic recovery of contractile function and suppression of the hypoxia- and reoxygenation-induced rise in resting tension. Hypoxia/reoxygenation-induced release of ATP metabolites was inhibited and restoration of myocardial high-energy phosphates enhanced. Inhibition of reoxygenation-induced rise in tissue calcium and sodium and creatine kinase release were also noted. The findings suggest that suppression of transmembrane flux of ions, substrates and enzymes during hypoxia/reoxygenation plays a role in the posthypoxic functional and metabolic recovery. Yohimbine (3-30 microM) significantly depressed the maximal stimulus frequency the left atria could follow. These results suggest a close relationship between depression in the maximal driving frequency of atria and enhancement of the posthypoxic contractile and metabolic recovery of perfused hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beneficial effects of yohimbine on posthypoxic recovery of cardiac function and myocardial metabolism in isolated perfused rabbit hearts. 167 45

The release of norepinephrine (NE) from the right atrium of the rabbit heart was used as a model to investigate biphasic effects due to tricyclic antidepressants, similar to those clinically observed in the treatment of depression and known as "therapeutic window". Strips of the atrium were loaded with 3H-NE, and then superfused by Krebs solution. The basal release and the electrical stimulation evoked release of 3H-NE were measured in the presence and absence of four clinically used tricyclic antidepressants: imipramine, amitriptyline, desipramine and nortriptyline. In addition, guanethidine, an adrenergic neuron blocker, was also studied. At lower concentrations (0.5-10 microM) tricyclic antidepressants increased, whereas higher concentrations (50-100 microM), inhibited the evoked release of NE. This inhibition was not prevented by the alpha2 adrenoceptor antagonist yohimbine, excluding the possibility of alpha 2 adrenoceptor-mediated inhibition of NE release. In higher concentrations the tricyclic antidepressants increased the basal release of NE in a Ca-independent way. Secondary amine derivatives were more potent inhibitors of the evoked release, and enhance the resting basal release of NE to a greater extent than the tertiary ones. Similarly, guanethidine (1-50 microM) also decreased the evoked release and increased the basal release of NE in a concentration dependent manner. Yohimbine failed to counteract the inhibition caused by guanethidine and the increment of the basal release was Ca-independent. It is concluded that the effect of tricyclic antidepressants in potentiating the release of NE is masked by their adrenergic neuron blocking properties, i.e. they inhibit the release of NE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biphasic effect of tricyclic antidepressants on the release of norepinephrine from the adrenergic nerves of the rabbit heart. 187 68

1. Norepinephrine (NE) and clonidine produce a phasic, dose-dependent contraction of the isolated guinea-pig terminal ileum. 2. The effect of NE was blocked by prazosin which produced a parallel rightward shift of the concentration-effect curve to NE, with a significant depression of maximum effects. 3. Yohimbine and indomethacin noncompetitively blocked, whereas practolol potentiated, the contractile effect of NE. 4. The contractile effect of clonidine was not antagonized by indomethacin or atropine. 5. These results suggest that the isolated guinea-pig terminal ileum has excitatory receptors sensitive to clonidine stimulation and excitatory alpha receptors sensitive to blockade by prazosin, and that the activation of the latter may be related to the activation of endogenous prostaglandin synthesis.
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PMID:Study of the contraction induced by norepinephrine and clonidine in the isolated guinea-pig ileum. 205 Feb 93

Antagonism of ketamine-xylazine (85 mg of ketamine/kg of body weight and 15 mg of xylazine/kg, IM) anesthesia in rats by yohimbine (YOH; 1, 5, 10, and 20 mg/kg, IP), tolazoline (TOL; 10, 20, or 50 mg/kg, IP), 4-aminopyridine (4-AP; 1 or 5 mg/kg, IP), or a combination of yohimbine and 4-aminopyridine (YOH:4-AP, 1 mg/kg:1 mg/kg or 5 mg/kg:1 mg/kg, IP) was studied. All dosages of YOH, TOL, 4-AP, and YOH:4-AP reduced the time to appearance of corneal and pedal reflexes. Only TOL was effective in reducing time to appearance of the crawl reflex and recovery time. Yohimbine, 4-AP, YOH:4-AP, and TOL were effective in reversing respiratory depression caused by ketamine-xylazine anesthesia, but anesthetic-induced hypothermia was not antagonized. When given to non-anesthetized rats, the antagonists had little influence on respiratory rate, but all antagonists caused significant (P less than 0.05) reduction in core body temperature for at least 90 minutes. When YOH was used as an anesthetic antagonist at dosage of 20 mg/kg, 20% mortality was observed and was attributable to acute respiratory arrest. The use of 4-AP and YOH:4-AP at the dosages studied induced moderate to severe muscular tremors. In conclusion, TOL at dosage of 20 mg/kg given IP, appears to be an appropriate antagonist for ketamine-xylazine anesthesia in rats.
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PMID:Antagonism of ketamine-xylazine anesthesia in rats by administration of yohimbine, tolazoline, or 4-aminopyridine. 205 29

1. Propagated Ca-spikes were recorded from isolated cervical sympathetic nerve trunks of the rat when bathed in a solution containing 5 mM Ca2+, 0.5 or 1 microM tetrodotoxin (to block Na currents) and 1 mM 4-aminopyridine (to reduce K currents). 2. Spikes persisted when external Ca2+ was replaced with Sr2+ or Ba2+, but were blocked by the addition of the following inorganic Ca-channel blockers (in descending order of potency): Cd2+ greater than La3+ greater than Ni2+ greater than Co2+ greater than Mn2+ greater than Mg2+. 3. Ca-spike amplitude was reduced by up to 90% by (-)-noradrenaline (IC50 1.5 microM). The following sympathomimetic amines imitated this effect (in descending order of potency): clonidine greater than or equal to (-)-adrenaline greater than or equal to [(-)-noradrenaline] greater than or equal to dopamine greater than (-)-phenylephrine greater than or equal to (+/-)-amidephrine. 4. Ca-spike inhibition by (-)-noradrenaline was antagonized by phentolamine (pA2 6.5). Yohimbine was about 10 times weaker than phentolamine; (+/-)-propranolol (1 microM) and prazosin (10 microM) had no clear effect. 5. (-)-Noradrenaline reduced the amplitude of the compound action potential recorded from the superior cervical sympathetic ganglion following supramaximal preganglionic trunk stimulation when recorded in normal Krebs solution and hyperpolarized the ganglion with respect to the post-ganglionic trunk. Depression of the transmitted ganglionic action potential was antagonized by phentolamine (5 microM) but not by yohimbine (1 microM); in contrast 1 microM yohimbine completely prevented the ganglionic hyperpolarization. (-)-Noradrenaline did not hyperpolarize the preganglionic cervical sympathetic nerve trunk under these recording conditions. 6. It is suggested that inhibition of transmitter release from sympathetic preganglionic fibres produced by noradrenaline results from a depression of the voltage-gated Ca current in the fibres and/or their terminals, and that this action is mediated by an alpha-adrenoceptor which does not fully conform to either alpha 1 or alpha 2 subtypes.
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PMID:Inhibition of Ca-spikes in rat preganglionic cervical sympathetic nerves by sympathomimetic amines. 253 83


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