PubMed Health⌕ Search

Biomedical subjects

S Bongrani

Publications and source records attributed to S Bongrani.

At least 37 records · Page 2Linked to original sources
PubMed1988

[Derivatives of pyrimidine 1,2-condensate. IV. Synthesis and pharmacological properties of the N,N-disubstituted 4-amino-2H-pyrido(1,2-a)pyrimidin- 2-ones and 2-amino-4H-pyrido(1,2-a)pyrmidin-4-ones].

The N,N-disubstituted 4-amino-2H-pyrido[1,2-a]pyrimidin-2-ones (III) and isomer 2-amino-4H-pyrido[1,2-a]pyrimidin-4-ones (IV) were obtained from the reaction of 2-aminopyridine with the N,N-disubstituted ethyl malonamate/phosphorus oxychloride reagent (II), in refluxing 1,2-dichloroethane. 2-[(N-Benzyl, N-ethyl)amino]derivative (IV b) was also prepared in excellent yield by treating 2-chloro-4H-pyrido[1,2-a]pyrimidin-4-one (V) with N-ethylbenzylamine. Finally, hydrogenation (Raney Nickel) of 4-[(N-ethyl,N-phenyl)amino]-2H-pyrido[1,2-a]pyrimidin-2-one (III e) afforded 6,7,8,9-tetrahydroderivative (VI) which in turn was treated with potassium borohydride to give 1,6,7,8,9,9a-hexahydroderivative (VII). Several compounds described in the present paper, along with some other compounds (III) and (IV) previously synthesized by us (1,2), were tested for various pharmacological activities. The antiallergic activity (PCA in the rat), even though found in several compounds examined, turned out to be submaximal in any case, in spite of the high dose administered (500 mg/kg p.o. as a rule). The most active compound (the activity being estimated at 0.42 times that of thiaramide hydrochloride) was the 4-aminoderivative (III e). The 2-aminoderivatives (IV) series, was found to have marked antiinflammatory properties (carrageenin oedema in the rat); nevertheless, this activity was related to toxic symptoms with the exception of compound (IV b), almost asymptomatic at the administered dose (200 mg/kg p.o.). Moreover the 2-aminoderivatives (IV) generally showed weak adrenolitic activity in vitro (rat seminal vesicles), which was estimated to be from 100 to 1000 times less than that of phenoxybenzamine.

Aminopyridines↗
PubMed1988

New pharmacological data on the bronchospasmolytic activity of bamifylline.

Resistance to lung inflation and blood pressure were monitored together with biological and radioimmunological determination of circulating thromboxane A2 (TxA2) in anaesthetized guinea-pig. Bamifylline, a 2-benzyl-[4,5-d]-imidazopyrimidine derivative, and theophylline were compared for their antagonistic activity against the pulmonary effect of histamine (0.05 mumol/kg i.v.), leukotriene C4 (LTC4, 0.016 mumol/kg i.v.), platelet-activating factor (PAF, 0.0002 mumol/kg i.v.) and acetylcholine (0.1 mumol/kg i.v.). Bamifylline, as well as theophylline, showed a dose-dependent antagonistic activity against both bronchoconstriction and TxA2 generation induced by the above agonists. However, except for histamine where the two compounds were equiactive, bamifylline was 2 times more potent than theophylline. The maximal inhibitory activity was found against bronchoconstriction induced by PAF (ED50 = 6.5 mumol/kg i.v.) followed by histamine (ED50 = 9.5 mumol/kg i.v.), acetylcholine (ED50 = 24.3 mumol/kg i.v.) and LTC4 (ED50 = 31.6 mumol/kg i.v.). Bamifylline (3, 10, 30, 100 mumol/kg i.v.) and theophylline (3, 10, 30, 100 mumol/kg i.v.) protected guinea-pig from antigen-induced bronchoconstriction and TxA2 generation in ovalbumin actively sensitized animals. Also in this series of experiments bamifylline was more potent than theophylline, the ED50 being 9.3 mumol/kg i.v. and 22.9 mumol/kg i.v., respectively. These pharmacological data represent new support for the protecting effect of bamifylline against respiratory damage induced by well known anaphylaxis mediators.

Acetylcholine↗
PubMed1985

Regional vasodilating and cardiac effects of nicardipine in anaesthetized open chest dog.

In this study the effects of intravenous nicardipine on the cardiovascular system in anaesthetized open chest dogs were assessed. In the dose range of 3-30 nmol/kg it induced a dose-dependent and long lasting reduction of the vertebral, coronary and femoral vascular resistance. Nicardipine proved to be equipotent, but longer lasting than nifedipine, and about 10 and 100 times more potent than verapamil and papaverine respectively. Unlike papaverine, calcium entry blockers caused a preferential vasodilation of the vertebral and coronary arteries. Hypotension and a reduction of LVSP and dP/dt appeared only at the highest dose tested. However, for both dihydropyridine derivatives, in contrast to verapamil, the cardiodepressant effects were short-lived and resulted less marked for nicardipine than for nifedipine.

Animals↗
PubMed1984

Beta-adrenoceptor and cyclo-oxygenase block as a tool for evoking the direct bronchoconstrictor effect of leukotriene C4 in the guinea-pig.

The intravenous administration of LTC4 to anaesthetized guinea-pigs induced dose-dependent bronchoconstriction, which was maximal at the dose of 1.6 nmol kg-1. The response was abolished by indomethacin. The maximal dose of LTC4, preceded by both (-)-propranolol and indomethacin, induced maximal, slow in onset and reversible broncho-constriction. This direct effect of LTC4 was markedly and long-lastingly antagonized by FPL-55712. The beta-blocker did not appreciably affect the systemic blood pressure changes induced by LTC4. The procedure described is suggested as a suitable tool for investigating the per se effect of leukotrienes on the guinea-pig airways in vivo, as well as the efficacy of their receptor antagonists.

Adrenergic beta-Antagonists↗
PubMed1984

In vitro effects of nicardipine on vascular and cardiac muscle preparations.

Nicardipine, a new 1,4-dihydropyridine derivative with Ca++-antagonist activity, was tested on rabbit aortic strips contracted with K+ and NA, and on an isolated guinea pig heart perfused at constant flow. It inhibited K+-contraction in the aortic strips and reduced coronary resistance with the same potency as nifedipine resulting about 10 time less potent than the latter in depressing the myocardial contractility. The effects of nicardipine appear to be related essentially to its Ca++-antagonist activity rather than to any antiphosphodiesterase activity.

Animals↗
PubMed1983

Beta 2-adrenoceptor blockade is the basis of guinea-pig bronchial hyper-responsiveness to leukotriene C4 and other agonists.

Four beta-adrenoceptor antagonists, namely (-)-propranolol, (+)-propranolol, ICI-118551 and (+/-)-practolol, were investigated for their effects on leukotriene C4 (LTC4)-induced bronchoconstriction in the anesthetized guinea-pig. (-)-Propranolol was also investigated for its effects on acetylcholine and histamine bronchospasm in the anaesthetized guinea-pig, and on LTC4-induced contractions of guinea-pig isolated trachea and lung parenchyma. The various beta-adrenoceptor antagonists potentiated, dose-dependently, the bronchoconstriction induced by threshold doses of LTC4 and the intensity of the potentiation correlated with the beta 2-blocking capacity possessed by the drugs. (-)-Propranolol potentiated the bronchospasm induced by threshold doses of acetylcholine and histamine but to a lesser degree than the LTC4-induced bronchospasm. The airway hyper-responsiveness induced by (-)-propranolol was unaffected by pretreatment with mepyramine, cyproheptadine, phenoxybenzamine, atropine or indomethacin. The airway hyper-responsiveness induced by (-)-propranolol persisted even in adrenalectomized or reserpine-treated guinea-pigs, although adrenalectomy induced some increase in airway responsiveness. (-)-Propranolol had no effect on LTC4, histamine and acetylcholine-induced contractions of isolated trachea and lung parenchyma. The results show that the airway hyper-responsiveness induced by beta-adrenoceptor antagonists generally correlates with their beta 2-blocking activity. The possibility remains that some other unknown mechanism(s) may also be implicated.

Adrenalectomy↗
PubMed1982

Investigation of the activity of bronchodilators using a simple but accurate inhalation procedure: forced insufflation.

A simple but accurate inhalation procedure for investigating the activity of antiasthmatic drugs is proposed. The procedure consists of the forced insufflation of the powdered drug, blended with micronised lactose, direct into the tracheobronchial tree. Beta-adrenoceptor agonists (isoproterenol and fenoterol) and antimuscarinics (atropine and ipratropium bromide) were tested using the method of Konzett and Rössler in the guinea-pig; their bronchodilator effects were tested both after forced insufflation and after intravenous administration. The proposed inhalation method supplied close-response curves qualitatively comparable to those obtained by the intravenous route, with the added advantage of more detailed information on the time-course effect. Forced insufflation may be the best procedure for investigating antiasthmatic drugs intended for use as inhalants.

Adrenergic beta-Agonists↗
PubMed1981

Quantification of the synergism between fenoterol and ipratropium bromide in the counteraction of experimental bronchospasm.

The interaction between the beta 2-agonist fenoterol and the antimuscarinic ipratropium bromide in the counter-action of experimental bronchospasm in the guinea-pig was studied qualitatively and quantitatively. Finney's analysis showed a significant overadditive interaction between the two constituents of the association, the 'overadditivity factor' being 2.15 if calculated on the peak activity or 2.68 if calculated on the area under the curve inhibition-time. In addition, the combination possesses both of the advantages of the two components, namely rapid onset of action (characteristic of the beta-agonist) and long duration of action (characteristic of the antimuscarinic). A study of the principal cardiovascular and hemodynamic parameters in the cat ruled out any synergism between the two drugs at these levels.

Acetylcholine↗
PubMed1981

Evidence of overadditive interaction between fenoterol and ipratropium bromide in the counteraction of cholinomimetic-induced tracheobronchial contractions.

A study was made of the pharmacological interaction between two bronchoselective antispasmodics, the beta2-agonist fenoterol and the antimuscarinic ipratropium bromide, in the counteraction of tracheobronchial smooth muscle contractions. Both the in vitro (isolated guinea-pig trachea stimulated by carbachol) and the in vivo experiments (bronchospasm induced by acetylcholine in the guinea-pig) pointed to an overadditive interaction. The evidence for a synergistic antagonism against cholinergic stimulation points to the potential value of the association between fenoterol and ipratropium bromide in the treatment of bronchial asthma, especially in view of the important role that the cholinergic system seemingly plays in this distance.

Airway Resistance↗
PubMed1980

[Phenoxybenzamine antagonism of ergometrine-induced increase of coronary artery resistance in rabbits].

Ergometrine is currently used as a test for Prinzmetal variant angina, causing specifically a coronary artery spasm in these patients, even if the mechanism of this drug on coronaries is still unclear. In isolated rabbit heart perfused at constant flow the administration of ergometrine at the concentration of 2.2 x 10(-5) M evoked a marked and longlasting increase of coronary resistance which was revealed by a rise in perfusion pressure from 68.2 +/- 12.9 to 124.4 +/- 21.7 (m +/- SD; n=21). This increase appears only with repeated perfusions of the drug and moreover it was not reproducible in the same preparation after its maximal response. The vasoconstriction was not significantly affected either by atropine or mepyramine, but it was strongly reduced by the phenoxybenzamine pretreatment (2.9 x 10(-6) M; n=8). It is evident the role of alpha-adrenergic receptors in ergometrine effect, but our results do not allow to understand its true mechanism, in fact the noradrenaline release can not be completely excluded.

Animals↗
PubMed1980

[Effect and action mechanism of hypothermia to preserve the ischaemic myocardium (author's transl)].

The ability of hypothermia (34 degrees, 28 degrees) to preserve cardiac metabolism and performance during ischemia, was evaluated in the isolated Langendorff perfused rabbit heart. The hearts, isolated and perfused aerobically for 20', were made ischemic for 90' and their wall temperature maintained either at 37 degrees, 34 degrees and 28 degrees. The hearts were consequently reperfused at 37 degrees for 30'. Some of the hearts were frozen and assayed for ATP and CP. Others were homogenized and their mitochondria harvest, using either an EDTA free or an EDTA-containing extraction medium. The oxidative phosphorylating and ATP generating capacity of these mitochondria were established and their Ca++ content determined. The mechanical performance of the hearts, which were paced, was monitored by means of an intra-ventricular balloon filled with water and connected with a pressure transducer. The hearts that were made ischemic and maintained at 37 degrees were severely depleted in ATP and CP content, their mitochondria accumulated Ca++ and their oxidative phosphorylating activity was impaired. During reperfusion mitochondrial Ca++ was substantially increased, the capacity of the mitochondria to use O2 for state III respiration was further impaired and their ATP generating capacity reduced. Diastolic pressure increased and there was no recovery of the ability of the hearts to develop sistolic pressure. The hearts made ischemic and maintained at 28 degrees were protected. There was a less marked rise in mitochondrial Ca++ concentration after ischemia and during reperfusion; the mitochondria recovered the capacity of utilizing O2 and of generating ATP. That was coincident with and almost complete recovery of mechanical performance. Hypothermia at 34 degrees during ischemia provoked only a partial protection. These results are discussed in accordance with the hypothesis that hypothermia protects heart muscle against the deleterious effects of ischemia not only by reducing the metabolic requirement but also by maintaining intracellular homeostasis with respect to Ca++.

Adenosine Triphosphate↗