Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the mouse isolated vas deferens the amplitude of excitatory junction potentials (e.j.p.s) recorded intracellularly from smooth muscle cells varied with the strength of stimulation. Receptor type selective opioids were tested in this preparation. The mu-agonist normorphine (2,000 nmol/l) reduced the amplitude of e.j.p.s and shifted the stimulus-response curve in a parallel way to the right. By contrast, the kappa-agonist U-50488 (1,000 nmol/l) and the delta-agonist [D-Ala2,D-Leu5]-enkephalin (2 nmol/l) caused a non-parallel shift of the curve. In addition, opioids having a lower selectivity for one type of receptor were also used. The preferential kappa-agonists ethylketocyclazocine (40 nmol/l) and dynorphin A1-13 (100 nmol/l) produced parallel and non-parallel shifts, respectively. Thus, normorphine and ethylketocyclazocine were more effective in depressing e.j.p.s evoked by low intensities of stimulation than those evoked by high intensities of stimulation. U-50488, dynorphin A1-13 and [D-Ala2,D-Leu5]-enkephalin caused an equal depression of e.j.p.s evoked by either intensity of stimulation. The preferential mu- and delta-antagonists naloxone (1,000 nmol/l) and ICI 154129 (10,000 nmol/l), reversed the action of the respective agonists normorphine and [D-Ala2, D-Leu5]-enkephalin. In addition, ICI 154129 (10,000 nmol/l) reversed the action of dynorphin A1-13, as well. The preferential kappa-antagonist MR-2266 (1,000 nmol/l) prevented the effect of both ethylketocyclazocine and U-50488. It is concluded that under the conditions of these experiments normorphine and ethylketocyclazocine acted at mu-, U-50488 at kappa-, and dynorphin A1-13 and [D-Ala2,D-Leu5]-enkephalin at delta-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Differential effect of stimulation strength in mouse vas deferens on inhibition of neuroeffector transmission by receptor type selective opioids. 286 18

The effects of acute intravenous administration of ICI 118,587 (Corwin), a partial beta 1 agonist, were studied in nine patients with dilated cardiomyopathy and symptomatic congestive heart failure. Hemodynamic and metabolic parameters were measured using Swan-Ganz, arterial, and coronary sinus catheters. Repeated doses of Corwin produced no significant change in left ventricular performance, while a trend towards decreased blood pressure and stroke work was seen. No change occurred in coronary sinus blood flow, transmyocardial lactate extraction, or catecholamine release. One patient had significant depression of left ventricular function with hypotension. Thus, acute infusion of Corwin produced no beneficial inotropic responses, but rather produced features suggestive of further myocardial depression.
 ...
PMID:Acute hemodynamic and metabolic effects of ICI 118,587 (Corwin), a selective partial beta 1 agonist, in patients with dilated cardiomyopathy. 286 73

The effects on left ventricular function and myocardial metabolism of Corwin (ICI 118,587), a selective beta-1 partial agonist, were evaluated in 12 patients with dilated cardiomyopathy. All patients were in sinus rhythm at the time of cardiac catheterization. Immediately before and 20 minutes after intravenous administration of 0.2 mg/kg Corwin over 2 minutes, high-fidelity left ventricular pressures and thermodilution coronary sinus blood flow were recorded along with ventriculograms in the 30 degrees right anterior oblique projection. In 11 patients, Corwin resulted in no change in heart rate, a fall in left ventricular end-diastolic pressure, a rise in left ventricular systolic pressure and an increase in cardiac index. There was a rise in both peak positive and peak negative dP/dt. End-diastolic and end-systolic volume indices fell, and ejection fraction rose. There was an increase in coronary sinus blood flow and a small rise in myocardial oxygen consumption. In contrast to these results in the group as a whole, in one patient Corwin produced depression of both systolic and diastolic left ventricular function. We conclude that, in many patients with dilated cardiomyopathy, Corwin produces an improvement in systolic and diastolic left ventricular function while at the same time only slightly increasing myocardial oxygen demand. In some patients, however, Corwin may result in a significant worsening of left ventricular performance due to its antagonistic effects.
 ...
PMID:[Acute effect of the cardioselective beta-1-partial agonist, Corwin, on ventricular function and myocardial oxygen consumption in patients with dilated cardiomyopathy]. 287 68

The effects of selective opioid receptor agonists and antagonists on neural discharge recorded from carotid body arterial chemoreceptors in vivo were studied in anaesthetized cats. Mean ID50 values were determined for each agonist and used to assess chemodepressant potency on intracarotid (i.c.) injection in animals artificially ventilated with air. [Met]enkephalin, [Leu]enkephalin, [D-Ala2, D-Leu5]enkephalin and [D-Pen2, D-Pen5]enkephalin were more potent chemodepressants than [D-Ala2, Me-Phe4, Gly-ol5]enkephalin, dynorphin (1-8) or ethylketocyclazocine; morphiceptin (mu-agonist) was inactive. The rank order of potency was compatible with the involvement of delta-opioid receptors in opioid-induced depression of chemosensory discharge. ICI 154129, a delta-opioid receptor antagonist, was used in fairly high doses and caused reversible dose-related antagonism of chemodepression induced by [Met]enkephalin. It also antagonized depression caused by single doses of [Leu]enkephalin, [D-Ala2, D-Leu5]enkephalin, [D-Ala2, Me-Phe4, Gly-ol5]enkephalin or dynorphin (1-8). ICI 174864, a more potent and selective delta-opioid receptor antagonist, also antagonized chemodepression induced by [Met]enkephalin or by the selective delta-receptor agonist [D-Pen2, D-Pen5]enkephalin. Comparison of background or 'spontaneous' chemosensory discharge during the 30 min periods immediately before and after injecting ICI 174864 (0.1-0.2 mg kg-1 i.c.) showed a significant increase in discharge in one experiment, but in four others discharge was either unaffected or decreased after the antagonist, which argues against a toxic depression of chemosensors by endogenous opioids under resting conditions in our preparation. Sensitivity of the carotid chemoreceptors to hypoxia (ventilating with 10% O2) was increased significantly after ICI 174864, which could be taken as evidence that endogenous opioids depress chemosensitivity during hypoxia. In contrast, responsiveness to hypercapnia was reduced after the antagonist, implying that endogenous opioids may potentiate chemoreceptor sensitivity during hypercapnia. The results obtained using 'selective' agonists and antagonists provide evidence that depression of chemosensory discharge caused by injected opioids involves a delta type of opioid receptor within the cat carotid body. Endogenous opioids may modulate arterial chemoreceptor sensitivity to physiological stimuli such as hypoxia and hypercapnia.
 ...
PMID:Characterization of opioid receptors in the cat carotid body involved in chemosensory depression in vivo. 287 62

Effects of a new selective beta1 partial agonist, ICI 118,587, on cardiac function were assessed in clinical settings. In 7 patients, responses to multistage treadmill exercise were studied before and after an acute intravenous injection of the drug. The heart rate and blood pressure were not altered by ICI 118,587 at rest but increases in both parameters in response to exercise were significantly reduced. Neither oxygen consumption nor plasma norepinephrine level was modified by the drug both at rest and during exercise. The long term effects of ICI 118,587 were assessed in 6 patients with mild to moderate cardiac failure consequent upon ischemic heart disease. After chronic administration of the drug exercise duration was increased. The symptom-limited maximal oxygen consumption increased by 16%, associated with prolongation of the exercise tolerance. In those patients who also had symptoms of angina pectoris, exercise levels which caused angina during the control study were tolerated without symptoms after ICI 118,587. Twelve patients with nocturnal bradycardia resulting from atrial fibrillation of sick sinus syndrome were treated with ICI 118,587. Monitoring of heart rate by 24-hour Holter ECG showed that ICI 118,587 increased minimal heart rate during sleep. Being a beta1-adrenoceptor partial agonist, it has both agonist and antagonist properties. Thus, ICI 118,587 buffers the heart from an excessively low sympathetic tone which may occur during sleep and from an excessively high tone during exercise. It appears to be of benefit in the treatment of mild to moderate cardiac failure consequent upon ischemic heart disease. It also improves oxygen demand-supply imbalance without inducing further myocardial depression or inappropriate bradycardia at rest. ICI 118,587 may therefore be described as a cardiostabilizer.
 ...
PMID:Cardiovascular effects of ICI 118,587, a new beta-adrenoceptor partial agonist in man. 287 3

In an attempt to identify possible beta-adrenergic mechanisms in the cat retina the authors extended their previous studies on the effects of beta-agonists (Graefe's Arch. clin. exp. Ophthalmol. 225: 33-38, 1987) to three beta-adrenergic antagonists: propranolol, ICI 118.551, and timolol were applied in micromolar concentrations to the arterially perfused, dark-adapted cat eye. The rod ERG b-wave was generally depressed, sometimes enhanced after initial depression (propranolol), without showing any clear-cut dose-dependency. In contrast, the rod-mediated optic nerve action potential exhibited dose-dependent depression of the plateau and OFF components. All effects were reversible within 60-80 minutes. These results, in conjunction with earlier data on the effects of beta-agonists and recent biochemical and autoradiographic studies, strongly support the theory that there are beta-adrenergic synaptic mechanisms located in the inner layers of the mammalian retina.
 ...
PMID:[Effect of beta-blockers on retinal function in vitro]. 290 Mar 47

Excitatory junction potentials (e.j.p.s) evoked by nerve stimulation were recorded from muscle cells of the rabbit isolated mesenteric artery. At 0.03 Hz the e.j.p. amplitudes were stable. When a train of fifteen pulses was applied at 0.25 Hz or at higher frequencies (0.5, 1 and 2 Hz), e.j.p.s showed an initial facilitation followed by depression. [Met5]enkephalin 0.1 and 1 mumol/l, [D-Ala2,D-Leu5]enkephalin 0.1 and 1, but not 0.01 mumol/l, and [D-Pen2, L-Pen5]enkephalin 3 mumol/l all depressed the e.j.p.s evoked by trains of fifteen pulses at 1 Hz. When more than one concentration was used ([Met5]enkephalin, [D-Ala2,D-Leu5]enkephalin), the inhibition was concentration dependent. It was always greater for the first few e.j.p.s than for the later ones in a train. [Met5]enkephalin 1 mumol/l reduced the first e.j.p. at 1 Hz and the e.j.p.s evoked by 0.03 Hz to a similar extent. The inhibitory effect of [Met5]enkephalin 1 mumol/l on e.j.p.s persisted in the presence of yohimbine 0.3 mumol/l. Naloxone 1 mumol/l did not interfere with the effect of [Met5]enkephalin 1 mumol/l. Naloxone 10 mumol/l depressed some e.j.p.s and prevented the inhibition by [Met5]enkephalin 1 mumol/l. Neither ICI 154129 10 mumol/l nor ICI 174864 0.3 mumol/l had any effect of their own and both compounds antagonized the action of [Met5]enkephalin 1 mumol/l. Normorphine 10 mumol/l, fentanyl 1 mumol/l, ethylketocyclazocine 0.1 mumol/l, and dynorphin A(1-13) 1 mumol/l were all ineffective. Ethylketocyclazocine 1 mumol/l did not change the e.j.p.s either, but antagonized [Met5]enkephalin 1 mumol/l. [Met5]enkephalin 1 mumol/l failed to influence both the resting membrane potential of the muscle cells and the depolarizing effect of noradrenaline 3 and 30 mumol/l. We suggest that the axon terminals of post-ganglionic sympathetic neurones in the rabbit mesenteric artery possess opioid delta-, but not mu- or kappa-receptors. The activation of presynaptic delta-receptors inhibits the release of the neuroeffector transmitter. There is no evidence for any effect of co-released endogenous opioid peptides under our experimental conditions.
 ...
PMID:Presynaptic opioid delta-receptors in the rabbit mesenteric artery. 303 Dec 83

Spinal reflexes in the rabbit are suppressed tonically by endogenous opioids. The contributions made to this suppression by mu-, delta- and kappa-opioid receptors have been investigated by studying the actions of a range of opioid antagonists and agonists on reflexes evoked by sural nerve stimulation in the ankle extensor gastrocnemius medialis (g.m.), and in the knee flexor semitendinosus (s.t.). When given at a total dose of 88.5 micrograms kg-1 i.v., either of the universal opioid receptor antagonists (-)-naloxone and (-)-quadazocine enhanced the g.m. response to more than 7 times the pre-drug control values, and the s.t. reflex to 1.5 times controls. The effects of quadazocine were stereospecific. The selective delta antagonist ICI 174864 (3.5 mg kg-1 i.v. total) also augmented the g.m. reflex but only to twice pre-drug controls. The mu-agonists fentanyl (100 micrograms kg-1) and morphine (50 mg kg-1) suppressed both g.m. and s.t. reflex responses to less than half control levels by a naloxone-reversible mechanism. The kappa-agonists bremazocine (50 micrograms kg-1 total), tifluadom (100 micrograms kg-1), ethylketocyclazocine (200 micrograms kg-1) and U50488H (1 mg kg-1) potentiated the g.m. reflex and had variable effects on the s.t. response. Naloxone usually added to the facilitatory actions of these drugs. kappa-Opioid receptor agonists also caused a profound, naloxone-reversible depression of arterial blood pressure. It may be concluded that the endogenous opioid-mediated suppression of spinal reflexes in the rabbit is mediated mainly, if not exclusively, through mu-receptors. There are no known endogenous ligands which are specific for the mu-receptor, so in the present case it seems that selectivity is determined by the receptor population rather than by the ligand.
 ...
PMID:The contributions of mu-, delta- and kappa-opioid receptors to the actions of endogenous opioids on spinal reflexes in the rabbit. 303 45

The mode of action of ICI 169,369, a novel 5-hydroxytryptamine2 (5-HT2) receptor antagonist, was investigated in arterial muscle. Isolated preparations from calf coronary artery and from rat tail artery with the endothelium rubbed off were set up to contract isometrically with 5-HT. ICI 169,369 (1-3000 nM) antagonized surmountably and competitively the contractile effects of 5-HT in coronary artery (pKB, 9.1) and tail artery (pKB, 8.8). Methysergide antagonized unsurmountably 5-HT-induced contractions by reducing maximum effects to 25% (coronary artery: pIC50, 9.8) and 60% (tail artery: pIC80, 9.0). ICI 169,369 (100-300 nM) restored the maximum effects of 5-HT that had been depressed by methysergide (20 nM coronary artery, 100 nM tail artery). Preincubation with ICI 169,369 also prevented the methysergide-induced depression of the maximum effects of 5-HT. The protective effect of ICI 169,369 was overcome by high methysergide concentrations (up to 3 microM), suggesting competition between the two drugs for a common site. The data are consistent with an allosterically modulated interconversion of the 5-HT2 receptor between two states (R in equilibrium R'). ICI 169,369 competes with 5-HT for the 5-HT2 receptor. ICI 169,369 and methysergide also compete for an allosteric site of the 5-HT2 receptor system, thereby facilitating the highly active R-state and low active R'-state, respectively.
 ...
PMID:ICI 169,369 is both a competitive antagonist and an allosteric activator of the arterial 5-hydroxytryptamine2 receptor system. 338 35

1 The actions of 4-(2-hydroxy-3-isopropylaminopropoxy) phenyl acetamide (ICI 66082), a new beta-adrenoceptor blocking drug, on the twitch response of the isolated papillary muscle of the rabbit and on dP/dt max and free heart rate of a denervated dog heart preparation, are described.2 ICI 66082 (up to 1 mg/ml) did not produce any depression of the twitch response of the rabbit papillary muscle. ICI 66082 antagonized the action of isoprenaline on this preparation at a concentration of 0.01 mug/ml.3 ICI 66082 (0.5-1.0 mg/kg intravenously) reduced the control value of dP/dt max in four dog preparations by a mean value of 529 mmHg/s (s.e. mean +/- 139 mm Hg/s), with no significant change in free heart rate. Antagonism of the effect of isoprenaline on dP/dt max and on free heart rate was demonstrated with ICI 66082 (0.1 mg/kg).4 ICI 66082 (1.0-1.5 mg/kg) produced no significant changes in dP/dt max or in free heart rate in four dogs pretreated with reserpine. A significant reduction (16% of the control value) in dP/dt max was observed with ICI 66082 at a high dose of 40-50 mg/kg.5 It is concluded that ICI 66082 is a competitive antagonist against the actions of isoprenaline on cardiac muscle, has no negative inotropic action (unless the dose exceeds 40 mg/kg) and lacks intrinsic sympathomimetic activity.
 ...
PMID:The actions of a new beta-adrenoceptor blocking drug, ICI 66082, on the rabbit papillary muscle and on the dog heart. 415 70


<< Previous 1 2 3 4 5 6 7 Next >>