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 propranolol, atenolol (ICI 66,082), practolol and pindolol on heart rate and maximal left ventricular dp/dt, atrioventricular conduction time, mean aortic flow and diastolic blood pressure during cardiac pacing were investigated over a wide dose range (0.025-4.0 mg/kg, i.v.) in dogs anaesthetized with pentobarbitone.2. Propranolol and atenolol produced similar reductions in haemodynamic parameters. Propranolol had no further effect in dogs pretreated with atenolol. 3. Practolol tended to cause smaller reductions in the haemodynamic parameters than either propranolol or atenolol. Subsequent administration of propranolol still had some depressant activity. 4. Pindolol produced a biphasic response, with depression of cardiac function at the low doses (0.025 and 0.1 mg/kg), but a reversal of effect as the dose was increased. 5. It is therefore concluded that, in anaesthetized dogs, the intrinsic activity of practolol and pindolol limits the fall in heart rate, cardiac conduction, aortic flow and maximal dp/dt observed with beta-adrenoceptor blockade. With pindolol, however, the influence of intrinsic activity is observed only in high doses related to beta-adrenoceptor blockade.
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PMID:The influence of the intrinsic sympathomimetic activity of beta-adrenoceptor antagonists on haemodynamic effects in anaesthetized dogs. 3 81

1. Responses of cerebral cortical neurones to the microiontophoretic application of acetylcholine, noradrenaline, cyclic adenosine 3',5'-monophosphate (cyclic AMP) and cyclic guanosine 3',5'-monophosphate (cyclic GMP) were examined.2. The application of acetylcholine and cyclic GMP to identified pyramidal tract neurones resulted in an increased frequency of firing in a large number of cells. Upon application of both substances to cells which could not be identified as pyramidal tract cells, a reduction in the frequency of spontaneous firing was sometimes observed.3. Careful current controls had no effect on the cells discussed here, indicating that the observed responses were not due to the iontophoretic currents. Also, the electro-osmotic ejection of cyclic GMP (outward current) produced similar changes of cell firing to those which followed iontophoretic application (inward current).4. The microiontophoretic application of atropine resulted in a blockade of acetylcholine responses while leaving responses to cyclic GMP unaffected. This suggests that cyclic GMP was not acting indirectly by releasing acetylcholine from presynaptic endings.5. Ejection of cyclic GMP from solutions containing calcium ions produced responses comparable to those produced by cyclic GMP alone. It is unlikely therefore that cyclic GMP was causing excitation by chelating calcium.6. Applications of noradrenaline and cyclic AMP produced a reduction in the spontaneous discharge rate of most neurones tested.7. Phosphodiesterase inhibitors such as ICI 63,197 caused a potentiation of the noradrenaline responses of pyramidal tract neurones.8. 5'-adenosine monophosphate produced a powerful depression of all cells to which it was applied. This action was blocked by aminophylline, suggesting the effect was mediated through an adenosine receptor. Responses to cyclic AMP were usually not abolished, but were reduced by about 50% in amplitude.9. These results are consistent with the hypothesis that cyclic AMP may mediate some neuronal effects of noradrenaline and cyclic GMP may mediate some effects of acetylcholine. The results are also consistent with the suggestion that the two nucleotides may sometimes mediate opposite cellular responses to humoral stimuli.
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PMID:Microiontophoretic studies of the effects of cylic nucleotides on excitability of neurones in the rat cerebral cortex. 19 28

During the last four years we have used a new cardioselective beta-adrenergic blocking substance, ICI 66.082 (atenolol or Tenormin), alone or in combination with other drugs for treatment of hypertension in a total of 104 patients, including 15 with a chronic obstructive lung disease. Fifty-one patients started treatment with atenolol because of side-effects--especially from the central nervous system--during previous treatment with non-selective beta-blockers, mostly propranolol (Inderal). Mean duration of treatment was 16 months (range 8--36) and mean dosage 163 mg/day. In 18 patients treatment with Tenormin was withdrawn, but only in 10 of them could this be referred to side-effects. Of the 51 patients who complained of or showed side-effects from another beta-blocker, 80% were improved after changing to Tenormin. Of the patients with side-effects from the central nervous system, 73% improved, especially those who complained of nightmares, hallucinations, insomnia or mild depression.
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PMID:Long-term clinical experience with atenolol--a new selective beta-1-blocker with few side-effects from the central nervous system. 36 88

Daily administration of 10 mg of Methallibure (ICI 33,828) for 6 days to male castrate rats resulted in significant depression of serum radioimmunoassayable luteinizing hormone (LH). Subsequent challenge with 100 ng of synthetic luteinizing hormone-releasing hormone (LHRH) showed these rats to release sufficient pituitary LH to achieve plasma levels equal to those of LHRH treated castrate controls. Although an effect at the level of the pituitary remains to be conclusively ruled out, these results suggest that the predominant in vivo effect of Methallibure in the castrate male rat is to suppress pituitary LH release due to diminished secretion of LHRH by the hypothalamus.
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PMID:The effects of Methallibure (ICI 33,828) on the LH release in castrate male rats challenged with LHRH. 109 6

The acute effects of ethanol (ETOH) on cardiac function in 32 normal subjects has been studied utilizing systolic time intervals. Seven (group I) 13 (group II), and 12 subjects (group III), reported an average daily consumption of less than 1 oz, 1-2 oz, and more than 2 oz of ETOH, respectively. Progressively higher control values from group I to group III in PEP, PEPI, ICT and PET/LVET were observed (PEP-I vs PEPI-III: P smaller than 0.05; PEP/LVET-I vs PEP/LVET-II and PEP/LVET-III: P smaller than 0.05). There was progressively less change in these variables following acute ETOH (P smaller than 0.02-0.05 in group I; P equals NS in group III, group II intermediate). This indicates some degree of chronic myocardial impairment in group II and especially in group III, which tends to be proportionate to the degree of chronic ETOH exposure. These data are not necessarily disparate with previous reports of little or even a salutary hemodynamic effect of ETOH in normal subjects. Thus, the relative stability of LVET post ETOH, coupled with the observed increase in heart rate, is consistent with previous reports of ETOH-induced rate-dependent increments in cardiac output with unchanging stroke volumes, in spite of the presence of acute myocardial depression. The observations reported herein demonstrate the probable incremental influence of ETOH consumption in a chain of events which may culminate in alcoholic cardiomyopathy.
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PMID:The basis for differences in ethanol-induced myocardial depression in normal subjects. 113 3

Hypogonadal (hpg) mutant mice, with a congenital deficiency of hypothalamic gonadotrophin-releasing hormone (GnRH), and testicular feminized (tfm) mice, which lack a functional androgen receptor, were used to study the effects of the potent GnRH agonist 'Zoladex' (ICI 118630; D-Ser (Bu(t))6, Azgly10-GnRH) on pituitary and gonadal function. Zoladex (0.5 mg) in a sustained-release lactide-glycolide copolymer depot was administered subcutaneously under anaesthesia and was left in place for 7 days, after which time the effects of the drug upon pituitary and serum gonadotrophin concentrations, glycoprotein hormone subunit mRNAs and testicular morphology were investigated. At the pituitary level, Zoladex treatment resulted in a substantial reduction in LH content in normal males, and LH content was depressed in hpg mice even below the basal levels normally found in these mutants. Pituitary LH content in the Zoladex-treated animals was depressed in the tfm groups, but not to the same levels as those found in the normal and castrated normal mice. Zoladex treatment at the time of castration prevented the post-operative elevation in serum LH associated with castration alone. In the androgen-deficient tfm mouse, Zoladex did not depress the normally elevated serum LH levels. Serum LH in the hpg animals was, in all cases, below the limit of detection of the assay. Pituitary FSH content was depressed into the hpg range in both the normal and castrated animals, but there was no further depression in the hpg mice. The pituitary content was reduced in the tfm mice, again the effects not being as dramatic as in the normal and castrated animals. Serum FSH content, as measured by radioimmunoassay, was depressed by 50% in normal mice; there was no reduction in the hpg mice, however. With regard to pituitary gonadotrophic hormone gene expression, Zoladex administration to normal mice caused a dramatic reduction in LH beta mRNA content, to a level approximating that found in untreated hpg mice. The drug also depressed LH beta mRNA in the castrated group to the hpg range when given at the time of castration, whereas in untreated castrated mice there was a significant increase in LH beta mRNA. In the tfm mouse, which can be considered as a model for long-term failure of androgen feedback, Zoladex again induced a fall in LH beta mRNA, but not to the same extent as in the normal and normal castrated group. Zoladex had no effect on the already low levels of LH beta mRNA found in hpg mice.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of the gonadotrophin-releasing hormone agonist 'Zoladex' upon pituitary and gonadal function in hypogonadal (hpg) male mice: a comparison with normal male and testicular feminized (tfm) mice. 138 60

Acute myocardial infarction with simultaneous occlusions of two main branches is very rare, and it is difficult to presume it before performing emergent CAG. We encountered two such cases recently. Case 1 was a 77 year-old woman. She was admitted to our hospital because of anterior chest pain. Emergent CAG disclosed complete occlusions of RCA-Segment 3 and LAD-Segment 7. ICT improved both of them to 90% stenoses. Case 2 was a 58 year-old man. He was admitted to our hospital because of upper abdominal pain. Emergent CAG disclosed complete occlusions of RCA-Segment 2 and LAD-Segment 6. ICT improved the former to 99% stenosis, and the latter recanalized. Myocardial dual scintigrams performed during the acute periods showed findings which were consistent with simultaneous occlusion of the two main branches in both cases. We could consider such reasons as coronary vasospasm, state of hyper-coagulability at the onset of myocardial infarction and depression of coronary pressure etc as possible causes of these cases.
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PMID:[Two cases of acute myocardial infarction with simultaneous occlusions of two main branches]. 156 87

1. ICI 170,809 (2-(2-dimethylamino-2-methylpropylthio)-3-phenylquinoline hydrochloride) is a potent 5-hydroxytryptamine (5-HT) type 2 postsynaptic receptor antagonist. 2. Effects of ICI 170,809 as single oral doses (3, 7, 15 and 30 mg) or placebo were studied on the duration of antagonism for the ex vivo platelet aggregatory response to 5-HT and to the pupillary light constrictor response in eight healthy male volunteers. 3. Pupillary dark adapted responses to a 0.5 s light stimulus were measured using a portable infrared pupillometer, for up to 24 h after dosing. 4. The in vitro platelet 5-HT aggregation response was reduced by ICI 170,809, with depression of the dose-response curve to 5-HT at all concentrations of 5-HT and with no evidence for a parallel shift. 5. The ex vivo platelet 5-HT response demonstrated a dose related significant (P less than 0.02) decrease in aggregation reaching a maximum at 2 h after dosing with the effect persisting for at least 8 h after dosing with the 7 and 15 mg doses. 6. Resting pupil diameter (RPD), and light induced pupillary responses in the dark adapted pupil, showed a significant (P less than 0.01) dose related reduction with significant (P less than 0.05) effects still present with the 15 and 30 mg doses at 8 h after dosing. 7. We conclude that, changes in both ex vivo platelet aggregation to 5-HT and dark adapted pupil size, are significantly correlated (P less than 0.0001) with log plasma concentrations (ng ml-1) of ICI 170,809, enabling the assessment of 5-HT2-receptor antagonism in man.
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PMID:The effects of a selective 5-HT2 receptor antagonist (ICI 170,809) on platelet aggregation and pupillary responses in healthy volunteers. 157 48

The cardiovascular and respiratory effects of dermorphin (D) have been evaluated in freely moving or anesthetized normotensive and spontaneously hypertensive male rats. Intravenously or intracerebroventricularly administration of D produced arterial hypotension with sinus bradycardia and respiratory depression. Naloxone antagonized the effects of D. Atrial natriuretic antipeptide IgG reduced the cardiovascular responses without any significant modification of respiratory response. ICI 174864, naloxonazine and binaltorphimine did not reduce the cardiovascular and respiratory effects. In hypertensive rats D produced more intense and longer cardiovascular effects than those seen in normotensive animals. D effects involve the activation of mu and k opioid receptors for cardiovascular responses and mu 2 opioid receptors for respiratory depression without any significant effect on delta receptors. The release of atrial natriuretic peptide also appears to be involved in the cardiovascular effects of D.
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PMID:Cardiovascular and respiratory effects of dermorphin in rats. 167 73

Use of selective delta opioid antagonists provide evidence that the delta receptor within the brain seems an integrated part in the mediation of respiratory depression induced by a potent analgesic like fentanyl. Low doses of the delta antagonists RX-8008M (3-6 micrograms/kg) as well as ICI 174,864 (3-6 micrograms/kg) reversed fentanyl-related respiratory depression (arterial blood gases) in the unanesthetized canine. Opioid-induced blockade of afferent sensory nerve volleys (amplitude height of the somatosensory-evoked potential) could be reversed only by a high dose (9 micrograms/kg) of RX-8008M. Depression of amplitude height of the SEP could not be reversed by ICI 174,864 over the whole dose range (3-6-9 micrograms/kg). In comparison, naloxone (1-5-10 micrograms/kg) not only reversed depression of PaO2, it also reversed the blockade of afferent sensory nerve impulses in the low (5-micrograms/kg)-dose range. A highly selective delta antagonist may have a therapeutic value in reversing opioid-related respiratory depression, resulting in little or no attenuation of analgesia.
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PMID:Opioid-induced respiratory depression and analgesia may be mediated by different subreceptors. 185 Aug 27


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