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. Experiments have been performed with the dual intent of analysing the mechanism by which AH 21-132 relaxes airways smooth muscle and determining whether the effects of this compound can be distinguished from those of theophylline. 2. AH 21-132 (0.25-8 microM) and theophylline (1-1000 microM) each caused concentration-dependent suppression of the spontaneous tone of guinea-pig isolated trachealis. The maximal effect of AH 21-132 was equivalent to that of theophylline. No evidence was obtained that the tissue became sensitized or desensitized to the action of AH 21-132. 3. Propranolol (1 microM) profoundly antagonized the tracheal relaxant action of isoprenaline but not that of AH 21-132. 4. In indomethacin (2.8 microM)-treated tissues, tone was induced by K+-rich (120 mM) Krebs solution, acetylcholine (ACh, 1 mM) or histamine (200 microM). Log concentration-relaxation curves for AH 21-132, isoprenaline and theophylline were all moved to the right in the presence of the spasmogens, the smallest rightward shift being induced by histamine and the greatest by ACh. While maximal effects of AH 21-132 and theophylline were unaffected by the spasmogens, that of isoprenaline was reduced by KCl and ACh. 5. In tissues treated with indomethacin (2.8 microM), AH 21-132 (0.1-100 microM) inhibited the spasmogenic effects of potassium chloride (KCl), ACh and histamine in a concentration-dependent manner. The inhibition was characterized by rightward shifts in the spasmogen concentration-effect curves with depression of their maxima. 6. In tissues treated with both indomethacin (2.8 microM) and ACh (1 mM), the removal of tracheal epithelium caused a small but significant leftward shift in the log concentration-relaxation curve for AH 21-132 but did not alter that for theophylline. 7. In tissues treated with indomethacin (2.8 microM) and maintained at 12 degrees C, theophylline (0.1-3.2 mM) caused concentration-dependent spasm. This effect was not shared by AH 21-132. 8. AH 21-132 (0.1-1000 microM) more potently inhibited the activity of cyclic AMP-dependent than of cyclic GMP-dependent phosphodiesterase derived from homogenates of guinea-pig trachealis. Theophylline, too, inhibited these enzymes but was less potent in each case than AH 21-132 and did not exhibit selectivity for the cyclic AMP-dependent enzyme. 9. It is concluded that AH 21-132 exerts a non-specific (i.e. effective no matter what agent is used to support tone) relaxant effect on the trachealis muscle which does not involve the activation of beta l-adrenoceptors. The profile of the relaxant action of AH 21-132 more closely resembles that of theophylline than that of isoprenaline. However, AH 21-132 can be differentiated from theophylline in that: (a) its relaxant potency is increased by epithelial removal; (b) it does not cause tracheal spasm; (c) it exhibits selectivity as an inhibitor of cyclic AMP-dependent as opposed to cyclic GMP-dependent phosphodiesterase. It is possible that the relaxant effects of AH 21-132 are related to its ability to inhibit cyclic nucleotide phosphodiesterases.
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PMID:Analysis of the relaxant effects of AH 21-132 in guinea-pig isolated trachealis. 255 42

The role of the vagus nerve and adrenoceptor stimulation in acid secretion after pylorus-ligation in the rat has been examined. All drugs were administered intraperitoneally. Atropine (5 mg kg-1) depressed the H+ output (111 mumols +/- 33.8 vs 412.5 mumols +/- 62.2, mean +/- s.e.m., n = 10, P less than 0.001); cimetidine (40 mg kg-1) did not enhance this action, while vagotomy was more effective than atropine (32.7 mumols +/- 4.9, mean +/- s.e.m., n = 10, P less than 0.05). Atropine (10 mg kg-1) produced a similar depression to the 5 mg kg-1 dose. Cimetidine (100 mg kg-1) depressed the H+ output (248.5 mumols +/- 46.8, mean +/- s.e.m., n = 10, P less than 0.05). Propranolol (5-20 mg kg-1) had no significant effect on the H+ output but dose-dependent inhibition was produced by phenoxybenzamine or phentolamine; an inhibition similar to that achieved by vagotomy was seen with the 20 mg kg-1 dose. Both these drugs (5 or 10 mg kg-1) had no significant effect on the H+ output when given with atropine (5 mg kg-1) but the H+ output was significantly lower than that produced by either drug at the same dose given alone. Atropine (5 mg kg-1) with phenoxybenzamine or phentolamine (20 mg kg-1) produced H+ output not significantly different from that with vagotomy or either alpha-adrenoceptor given alone at 20 mg kg-1, but the result was significantly (P less than 0.05) lower than the H+ output with atropine (5 mg kg-1) alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of vagal adrenergic activity in the mechanism of gastric acid secretion after pylorus-ligation in the rat. 257 4

We examined the effects of adrenaline on the noradrenaline release rate and plasma catecholamine levels in the pithed rabbit with electrically stimulated sympathetic outflow (3 Hz). Adrenaline (0.06 micrograms/kg/min) increased the rate of noradrenaline release into the plasma. This increase was prevented by propranolol (0.2 mg/kg + 0.1 mg/kg/h) and probably involves activation of presynaptic beta-adrenoceptors. A higher dose of adrenaline (1.0 micrograms/kg/min) significantly reduced the noradrenaline release rate. The reduction was "reversed" to a facilitatory effect by phenoxybenzamine (4 mg/kg). Propranolol alone slightly inhibited the noradrenaline release rate. After pretreatment with desipramine (1.0 mg/kg + 0.2 mg/kg/h), the inhibitory effect of propranolol on noradrenaline release was more pronounced and blood pressure was also lowered. However, in rabbits pretreated with captopril (1 mg/kg) in addition to desipramine, the sympathoinhibitory effect of propranolol was not observed. These results suggest that adrenaline can activate either presynaptic beta-adrenoceptors to increase noradrenaline release or, in higher doses, presynaptic alpha-adrenoceptors to inhibit noradrenaline release in vivo. The decrease in the noradrenaline release rate produced by propranolol alone may not be due to blockade of facilitatory presynaptic beta-adrenoceptors, but rather to depression of renin secretion. This would decrease angiotensin II formation and hence decrease the presynaptic release-enhancing effect of angiotensin II.
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PMID:Dual effect of adrenaline on noradrenaline release in the pithed rabbit. 258 Oct 76

A placebo-controlled, double-blind, crossover study was conducted to determine the effects of nifedipine (60 to 90 mg per day) monotherapy and propranolol (240 mg per day) monotherapy on symptoms, angina threshold, and cardiac function in patients with chronic stable angina. Following a two-week placebo period, patients were randomly assigned to receive either nifedipine or propranolol for a five-week treatment period, after which they crossed over to the alternative regimen. All 21 patients were men with chronic stable angina pectoris, 13 of whom had symptoms both at rest and on exertion. New York Heart Association functional class improved in patients taking either nifedipine or propranolol, and nitroglycerin consumption decreased with both treatments compared with placebo. Nifedipine significantly delayed the onset of chest pain and 1 mm of ST-segment depression during bicycle exercise; increases with propranolol were smaller and not statistically significant. Nine patients had a preferential clinical response to nifedipine compared with six patients to propranolol; this was unrelated to the presence or absence of pain at rest or to any baseline hemodynamic finding. Nifedipine and propranolol were equally effective in relieving exertional ischemia as shown by improvement in radionuclide ejection fraction at identical work loads. Exercise wall motion, assessed by a semiquantitative wall motion score, also improved with both drugs. Propranolol treatment decreased exercise cardiac output by 14 percent (p = 0.01) through its effect on heart rate. In contrast, nifedipine treatment had no effect on cardiac output. Thus, nifedipine is more effective on several measurements than propranolol when administered as single drug therapy in stable angina and has the advantage of preserving cardiac output during exercise.
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PMID:Chronic stable angina monotherapy. Nifedipine versus propranolol. 264 28

The influence of cold on the threshold for myocardial ischemia and the efficacy of antianginal drugs in a cold environment were assessed in 24 patients with stable angina and exercise-induced ST depression. Treadmill exercise tests were done according to a randomized double-blind protocol 90 minutes after administration of placebo, 80 mg propranolol, or 120 mg diltiazem, each at both -8 degrees and 20 degrees C. Eight of the patients were classified by history as cold-sensitive before the study. For the entire group, none of the exercise end points differed significantly between cold and normal temperatures with placebo. However, cold-sensitive patients developed 1 mm ST depression 30% sooner (169 +/- 41 versus 244 +/- 38 seconds, p less than 0.01) at -8 degrees C compared with 20 degrees C. At the onset of ischemia, rate-pressure product was lower in the cold (19.8 +/- 1.0 versus 22.0 +/- 1.6 x 10(-3), p less than 0.05). Both propranolol and diltiazem prolonged time to onset of 1 mm ST depression at both temperatures. The magnitude of improvement at -8 degrees C was equal to that at 20 degrees C, and differences between the two drugs were not statistically significant. Only diltiazem prolonged total exercise duration. Thus, as assessed by exercise testing, cold does not worsen ischemic threshold in most stable angina patients. However, in a subgroup identifiable by history, ischemic threshold is lower in the cold. Propranolol and diltiazem are as effective for exercise-induced ischemia in a cold environment as at normal temperatures.
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PMID:Exercise-induced myocardial ischemia in a cold environment. Effect of antianginal medications. 271 70

The participation of presynaptic adrenoceptors and receptors mediating the postsynaptic excitatory junction potential (e.j.p.) responses in feedback regulation of neurotransmission in the guinea-pig saphenous artery was studied by electrophysiological recording of the synaptic potentials. Stimulation of perivascular nerves elicited e.j.p. and slow depolarization in the artery. With repetitive stimulation, the successive e.j.p.s decreased in amplitude. Prazosin abolished the slow depolarization without any effect on the e.j.p. The depression of e.j.p. with repetitive stimulation was converted to facilitation in the presence of yohimbine. Yohimbine inhibited the first e.j.p. in a train but did not have a significant effect on the slow depolarization and contraction. A high concentration of ANAPP3, a specific P2-antagonist, depressed the e.j.p. The slow depolarization and contraction, however, were significantly potentiated by ANAPP3, even at low concentrations. Propranolol had no effect on the neural responses. The results suggest that there are functional presynaptic alpha 2-adrenoceptors and P2-receptors that could play a physiological role in the autoregulation of neuromuscular transmission in the guinea-pig saphenous artery.
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PMID:Autoregulation of neuromuscular transmission in the guinea-pig saphenous artery. 282 Jul 58

This paper reviews briefly the very common finding in chronic antidepressant use, of subsensitivity of the beta-adrenoreceptor-linked cyclic AMP system. This subsensitivity is observed with a number of different antidepressant treatments, including pharmacological, electrical and sleep deprivation. The subsensitivity requires intact noradrenergic and serotonergic systems, functionally linking the two neurotransmitters most often implicated in depression. Thyroid hormones and estrogens also cause subsensitivity, while the opposite effect is seen with Reserpine and Propranolol. A modified conditioning/sensitization model is proposed, implicating psychosocial stressors with a biological inability to down-regulate beta-adrenoreceptors.
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PMID:The antidepressant effect of beta-adrenoreceptor subsensitivity: a brief review and clinical implications. 283 4

Intravenous amitraz caused significant hypotension and bradycardia in pentobarbitone anaesthetized guinea-pigs. Depression of blood pressure reached a plateau with a dose of 10 mg/kg but heart rate continued to fall in a dose-dependent manner, up to a fall of 90 beats per minute after a total of 160 mg/kg/min. Amitraz was then tested on spontaneously beating guinea-pig isolated atria. The maximum bath concentration approximated a blood concentration produced by 5 mg/kg amitraz in the guinea-pig (2.3 X 10(-4) M). Amitraz did not significantly shift the dose-response curve to isoprenaline or acetylcholine but antagonized histamine rate responses competitively in the presence of propranolol (2 X 10(-6) M). Propranolol unmasked a dose-dependent depressant effect of amitraz on atrial rate, an effect abolished with atropine (1 X 10(-5) M). Amitraz increased atrial force of contraction, an effect which was not seen when propranolol was present in the bath solution. Amitraz also depressed atrial rate directly, but this effect was minor in comparison to bradycardia seen in the guinea-pig. It is likely that the cardiovascular depression seen in the guinea-pig following amitraz i.v. is caused by an alteration in autonomic drive rather than a significant direct cardiac effect.
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PMID:The cardiac effects of amitraz in the guinea-pig in vivo and in vitro. 287 7

The interaction between beta-adrenoreceptor blockers and calcium antagonists may occasionally be dangerous. The effects of the new calcium antagonist PN 200-110 (isradipine) were compared with those of verapamil in 3 groups of conscious rabbits pretreated with either pindolol 0.3 mg/kg, propranolol 1 mg/kg intravenously or placebo. Each animal received PN 200-110 (0.01, 0.03 and 0.1 mg/kg) and 2 or more days later verapamil (0.1, 0.3 and 1 mg/kg). The calcium antagonists were given to lower mean blood pressure to the same extent as in the placebo group. This blood pressure effect remained unchanged after pretreatment with pindolol or propranolol. Both PIN 200-110 and verapamil increased heart rate to the same extent as in the placebo group. Both beta blockers blunted the effect of PN 200-110 on heart rate but converted the verapamil-induced tachycardia to bradycardia. Propranolol blunted the PN 200-110-induced increase in cardiac output and total peripheral conductance, whereas the high verapamil dose decreased cardiac output and caused peripheral vasoconstriction in propranolol-pretreated animals. Thus, both agents lowered blood pressure by peripheral vasodilatation in the placebo group, after beta blockade; however, the mechanism of the verapamil-induced blood pressure decrease changed from pure vasodilation to a decrease in cardiac output, i.e., cardiac depression. Verapamil but not PN 200-110 prolonged the PQ interval, especially in animals who had received beta blockade. Most differences in the interaction were attributable to differences between the 2 calcium antagonists; the differences between the beta blockers were small and in favor of pindolol.
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PMID:Interaction between two calcium antagonists and two beta blockers in conscious rabbits: hemodynamic consequences of differing cardiodepressant properties. 288 Apr 95

Studies evaluating the antianxiety and antipanic properties of beta-blockers do not support their routine use in treating either generalized anxiety disorder or panic disorder. The use of propranolol for anxiety disorders accompanied by physical symptoms, especially cardiovascular complaints, may be effective in some patients when combined with benzodiazepines or perhaps in some non-responders to conventional treatment. Better designed studies are needed to evaluate the exact role of beta-blocking agents in treating anxiety. The efficacy of propranolol in patients with panic disorder has not been widely researched, but preliminary results have not been encouraging. Propranolol may provide symptomatic relief in some patients with residual somatic complaints (i.e., palpitations and tachycardia), when combined with the patient's ongoing drug regimen. Because beta-blockers may induce depression, they should be used cautiously--if at all--in panic patients with concurrent depressive illness.
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PMID:Beta-blockers in anxiety disorders. 289 Jun 77


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