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Biomedical subjects

C G Persson

Publications and source records attributed to C G Persson.

At least 199 records · Page 11Linked to original sources
PubMed1982

Xanthine derivatives as adenosine receptor antagonists.

The potency of a series of xanthine derivatives as adenosine antagonists was studied in fat cells (A1-receptors) and hippocampal slices (A2-receptors) and on L-[3H]phenylisopropyladenosine (PIA) binding in membranes from rat cortex. The order of potency in all three tests systems was: diethyl-8-phenyl-theophylline greater than 8-phenyltheophylline greater than 8-p-sulfophenyltheophylline greater than verrophylline greater than isobutylmethylxanthine greater than theophylline caffeine greater than theobromine. Enprofylline was about 20 times more potent in the hippocampus system than in the other two systems.

Adipose Tissue↗
PubMed1982

Differentiation between bronchodilation and universal adenosine antagonism among xanthine derivatives.

Relaxant effects and adenosine-antagonism of 3-propyl-xanthine (enprofylline) and 10 different methyl-xanthines were examined in isolated guinea-pig tracheas. The chemical structural requirements for tracheal relaxation were found to be different from those for adenosine antagonism by the xanthine derivatives. All xanthines produced relaxation: Enprofylline was about 5 times more potent than theophylline. However, only xanthines with a methyl in the 1-position consistently antagonized the relaxant effect of adenosine. --Theophylline over a wide range of concentrations (30-900 microM) produced a concentration dependent and surmountable antagonism at nervous adenosine receptors (isolated guinea-pig myenteric-plexus preparations). The same concentrations of enprofylline were almost devoid of antagonism at these adenosine receptors. In mice theophylline (6-24 mg/kg given intraperitoneally) dose-dependently increased locomotor activity while enprofylline (2-48 mg/Kg) was without effect on behaviour. "Non-blocking" xanthines such as enprofylline may be potent bronchodilators but lack many theophylline-like actions. We, therefore, forward the hypothesis that universal adenosine antagonism is both unnecessary and undesirable with xanthine antiasthmatics.

Adenosine↗
PubMed1982

Effects of enprofylline, a xanthine lacking adenosine receptor antagonism, in patients with chronic obstructive lung disease.

Enprofylline, a xanthine-derivative shown experimentally to lack universal adenosine receptor antagonism, has been examined in patients with partly reversible, chronic, obstructive lung disease. Significant bronchodilation was produced by enprofylline 2 mg/kg, giving a peak plasma concentration of 3.0 +/- 0.6 microgram/ml (mean +/- SD). A dose of 2 + 4 mg/kg dilated the bronchi at least to the same extent as theophylline 9.2 +/- 0.9 mg/kg (plasma level 18.5 +/- 4.7 micrograms/ml). Neither at the low nor at the high dosage (2 +/- 4 mg/kg), giving plasma concentrations of 8.5 +/- 1.4 microgram/ml, did enprofylline produce theophylline-like CNS effects, such as restlessness and tremor, but it did exhibit some of the innocuous side effects expected with xanthine derivatives, such as epigastric discomfort and headache. The comparison with theophylline was limited because different dosage forms had to be used (solution an tablets), which for example, resulted in different absorption rates. Nevertheless, the present findings indicate enprofylline to be potent bronchodilator in patients with obstructive lung disease, suggesting that adenosine-receptor antagonism is not involved in the bronchodilator effects of xanthines.

Adult↗
PubMed1982

Universal adenosine receptor antagonism is neither necessary nor desirable with xanthine antiasthmatics.

The great diversity of pharmacological effects of xanthines may well reflect different cellular mechanisms of action. Major attention is presently devoted to adenosine receptor antagonism that, in contrast to phosphodiesterase inhibition, is clearly produced by therapeutic concentrations of theophylline. The ubiquitous adenosine effects together with the universal and potent blocking action of methylxanthines have led investigators to believe that most pharmacological actions including antiasthmatic effects of theophylline reflect adenosine antagonism. The present hypothesis proposes that universal adenosine receptor antagonism is neither necessary nor desirable with xanthine antiasthmatics. Supporting the hypothesis a xanthine derivative that seems to be devoid of functional effects at important adenosine receptor sites has been shown to be a potent bronchodilator drug that lacks theophylline-like diuretic and CNS-stimulant behavioural effects.

Adenosine↗
PubMed1982

Some beta-adrenoceptor functions of the therapeutic interest.

The availability of selective beta-receptor agonists such as terbutaline is a stimulus to research dealing with various beta-receptor functions. The aim of such work is to demonstrate the physiological importance of the hormonal or nervous activation of receptors and to establish a scientific basis for therapeutic trials with beta-receptor active drugs. A brief account is given of the therapeutic possibilities as related to certain beta-receptor functions in the biliary tract, the urinary tract, the lung and the uterus. It is concluded that many beta-receptor functions can be described as therapeutically interesting. The practical importance of beta-agonist therapy is at present confined to relatively few organs, in particular the lung and the uterus.

Adrenergic beta-Agonists↗
PubMed1982

Seizure activity in animals given enprofylline and theophylline, two xanthines with partly different mechanisms of action.

Theophylline, that is a potent adenosine receptor antagonist, and enprofylline (3-propylxanthine), that seems to lack antagonism of neuronal depressant effects of adenosine, have been tested for convulsive activity in three animal species. In urethane-anaesthetized guinea-pigs theophylline produced massive generalized convulsions. Enprofylline was without any seizure activity but produced about the same changes as theophylline in heart rate, blood pressure, respiratory rate (less marked) and blood gas status. The lethal infused dose of enprofylline ws about twice as large as that of theophylline. This should be compared with the observation that enprofylline is about 5 times more potent than theophylline as a bronchodilator. Also in conscious guniea-pigs, mice and cats enprofylline was shown to be devoid of theophylline-like seizure activity. The CNS-stimulant effects of lethal doses of theophylline progressed until death occurred. The major behavioral effects of lethal doses of enprofylline in contrast were inhibition of activity and sedation. It is suggested that lack of seizure-activity reflects inability of enprofylline to antagonize neuronal depressant effects of endogenous adenosine.

Animals↗
PubMed1981

Influence of tracheal contraction on relaxant effects in vitro of theophylline and isoprenaline.

1 Relaxation by (-)-isoprenaline (Iso) and theophylline (Theo) was measured in guinea-pig isolated trachea, in the presence or absence of carbachol. 2 With basal tone or with carbachol at a concentration of 5.4 x 10(-7) M, causing 70% maximal contraction, Iso and Theo relaxed the trachea to the same extent. 3 With carbachol concentrations of 5.4 x 10(-6) M and 5.4 x 10(-5) M (96% and 100% maximal contractions) Iso caused no more than 63% and 34%, respectively, of the maximum relaxation to Theo. 4 When calculated at 25% of the maximum Theo relaxation, the Iso/Theo potency ratio was gradually reduced from 14,160 when evaluated at basal tone to 1,560 at the highest carbachol concentration. 5 In combination, at their maximally effective concentrations, Theo and Iso produced no larger a relaxation than did Theo alone. 6 At the two highest concentrations of carbachol, concentration-response curves to Theo were virtually superimposable whether determined in the absence or the presence of Iso at its maximally effective concentration. 7 It is concluded that Theo causes a greater relaxation of highly contracted tracheal muscle than Iso.

Airway Resistance↗
PubMed1981

Convulsive effect of theophylline in conscious and anaesthetized guinea-pigs.

In urethane-anaesthetized guinea-pigs, the effect of theophylline (theo) on heart rate, arterial blood pressure, respiration rate and limb movements were recorded. Continuous intravenous infusion of theo initially increased the respiratory and heart rates and lowered the arterial blood pressure. After infusion of about 50 mg/kg of theo, the cardiovascular effects reached a maximum and were then only slightly changed until the terminal stage. A tonic stretching of the limbs (at 155 +/- 15 mg/kg) preceded generalized seizures of clonic tonic convulsions which were recorded after infusion of 367 +/- 25 mg/kg of theo. At this stage, respiration was highly irregular. PaO2 started to fall and PaCO2 to rise, while a plasma acidosis developed rapidly. The convulsions progressed in frequency and intensity and were terminally associated with respiratory and cardiovascular collapse. The convulsive effects of theophylline were similar to those observed in conscious guinea-pigs after 250 mg/kg of theo orally. The present findings agree with the view that the convulsive effect is a primary life-threatening action of theophylline. The method described may be of use in the search for new, less toxic xanthine drugs.

Administration, Oral↗
PubMed1980

Extrapulmonary effects of theophylline.

The phamacodynamics of theophylline including cardiovascular and renal effects, effects on the CNS, gastrointestinal tract and uterus and the metabolic actions of the drug are reviewed. Emphasis is given to the clinical consequences of these effects.

Central Nervous System↗
PubMed1980

Some pharmacological aspects of xanthines in asthma.

Xanthines, best represented by theophylline, constitute a pharmacological principle of considerable age and importance in the treatment of asthma. Historical aspects of xanthines, effects of these compounds in the lung, and xanthine drug research are briefly reviewed. Data are presented on the active metabolite of theophylline, on relaxant effects of theophylline in large and small human respiratory airways, and on anti-edema effects of theophylline.

Asthma↗
PubMed1979

Terbutaline and adrenaline inhibit leakage of fluid and protein in guinea-pig lung.

The effect of terbutaline (0.3 mg/kg s.c.) and adrenaline (0.1 and 0.3 mg/kg s.c.) on histamine--aerosol-induced increase in lung weight and dye content was studied in conscious guinea pigs, previously given Evans blue dye. Both drugs prevented the effects of histamine. It is concluded that terbutaline and adrenaline have a pronounced anti-permeability effect in guinea-pig lungs inhibiting the histamine-induced microvascular efflux of fluid and protein.

Aerosols↗
PubMed1979

Anti-anaphylactic and bronchodilating action of a beta-adrenoceptor stimulator, KWD 2131, in human lung tissue.

The beta-adrenoceptor stimulating agent KWD 2131 has been studied with regard to inhibitory effect on allergen-induced histamine release from passively sensitized human lung tissue and relaxing effect on contracted small (diameter = 1 mm) and large (diameter greater than 3 mm) isolated human bronchi. The dose for 50% inhibition of the allergen-induced histamine release was 2 x 10(-11) M. The potency of KWD 2131 was approximately 0.15 times that of terbutaline and 0.05 times that of isoprenaline in this respect. The bronchodilating potency of KWD 2131 was 0.02-0.03 times that of terbutaline. The data indicate that KWD 2131 is a compound with preferably anti-anaphylactic potency in the human lung.

Adrenergic beta-Agonists↗
PubMed1979

Vascular anti-permeability effects of beta-receptor agonists and theophylline in the lung.

In conscious guinea-pigs the effect of theophylline, terbutaline and isoprenaline on histamine-induced increase in lung weight was examined. Animals exposed to a saline aerosol had a lung weight to body weight ratio of about 0.8%. Exposure to a histamine aerosol raised this value to about 1.1 (P less than 0.001). Theophylline 55 mg/kg and 110 mg/kg was given orally, terbutaline 0.1 mg/kg and isoprenaline 0.01 mg/kg and 0.03 mg/kg subcutaneously before exposure to histamine. The three drugs prevented the lung weight effect produced by histamine aerosol (P less than 0.01, P less than 0.001, P less than 0.001, P less than 0.1, P less than 0.001 respectively). Changes in lung blood content did not contribute to the weight-reducing effects. The potency ratio found between terbutaline and isoprenaline suggests that beta-2-receptors might be involved in the anti-permeability effect. Propranolol-treated animals did not survive in the histamine-aerosol unless they received theophylline; neither bronchodilator nor antipermeability effects of theophylline were antagonized by propranolol. It is concluded that in guinea-pigs theophylline and beta-agonists, in bronchodilating doses have the additional effect of preventing permeability oedema in the lung.

Administration, Oral↗
PubMed1979

Relaxant effects of nifedipine on isolated, human myometrium.

Myometrial tissue was obtained from non-pregnant women subjected to hysterectomy because of various gynaecological disorders, and from women undergoing caesarean section. Strip preparations were dissected and isometric tension was recorded. Nifedipine (2.9 X 10(-8)--2.9 X 10(-6)M) inhibited spontaneous contractile activity, mainly by reducing the amplitude of contraction in both non-pregnant and pregnant myometrium. The drug also inhibited potassium induced contractions in a concentration dependent manner. This effect seemed to be more pronounced in pregnant than in non-pregnant tissue. In preparations of pregnant human myometrium, normally polarized or potassium depolarized, oxytocin induced a contractile activity that was effectively inhibited by nifedipine. Nifedipine also relaxed contractions induced by vasopressin in isolated non-pregnant myometrium. It is concluded that the relaxant effect of nifedipine on isolated pregnant and non-pregnant human myometrium can be explained by inhibition of calcium influx. The results thus support the view, that calcium influx is an important step in the initiation of contractile activity in human uterine smooth muscle.

Adult↗