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Biomedical subjects

E Marmo

Publications and source records attributed to E Marmo.

At least 37 records · Page 2Linked to original sources
PubMed1990

1-phenyl-1H-pyrazole derivatives with antiinflammatory, analgesic and antipiretic activities.

Reaction of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates 2 with phenylhydrazine gave the corresponding esters of 5-substituted 1-phenyl-1H-pyrazole-4-carboxylic acids 3 in high yields. Esters 3 were hydrolyzed to the relative carboxylic acids 4, which were converted by heating to 5-substituted 1-phenyl-1H-pyrazoles 5 in excellent yields. Reaction of methyl 5,5-dimethyl-3-dimethylaminomethylene-2,4-dioxohexanoate with phenylhydrazine afforded methyl 1-phenyl-4-pivaloyl-1H-pyrazole-5-carboxylate 8 b, which was converted as above to the corresponding carboxylic acid 10 b and this to 1-phenyl-4-pivaloyl-1H-pyrazole 11 b. Starting from 5-methoxymethyl-1-phenyl-1H-pyrazole, 1-phenyl-1H-pyrazole-5-acetic acid 18 and its alpha-methyl derivative 19 were also synthesized. Compounds 18, 19, 10 b and 11 b showed a strong antiinflammatory activity in rats; the same compounds in general as well as 8 b, showed appreciable analgesic and antipyretic activities in mice and rats, respectively.

Animals↗
PubMed1990

Omega-dialkylaminoalkyl ethers of 3-exo-dialkylamino-(Z)-camphoroximes with antiarrhythmic and local anesthetic activities.

The synthesis of 3-exo-dialkylamino-(Z)-camphoroximes 7 starting from a mixture of 3-endo- and 3-exo-bromocamphornitrimine, hydroxylamine hydrochloride and excess secondary amine (dimethylamine, pyrrolidine, piperidine or morpholine) is described. Compounds 7 gave a series of omega-dialkylaminoalkyl ethers 9, 10 and 11 by reaction of 7 as sodium salts with omega-chloroalkyldialkylamines in DMF solution. Some of compounds 9, 10, 11 showed an appreciable antiarrhythmic and local anesthetic activity in rats and mice, respectively.

Amines↗
PubMed1990

3,5-Diphenyl-1H-pyrazole derivatives. VI--Esters and 2-dialkylaminoethyl ethers of 1(2-hydroxy-2-phenylethyl)-3,5-diphenyl-1H-pyrazole and N,N-disubstituted 1-(2-amino-2-phenylethyl)-3,5-diphenyl-1H-pyrazoles with depressant and platelet antiaggregating activities.

The syntheses of 1-(2-hydroxy-2-phenylethyl)-3,5-diphenyl-1H-pyrazole 1 by reaction of 2-hydrazino-1-phenylethanol with dibenzoylmethane, of esters 2 and 2-dialkylaminoethyl ethers 3 starting from 1 as sodium salt and acyl chlorides or 2-chloroethyldialkylamines, respectively, as well as of N,N-disubstituted 1-(2-amino-2-phenylethyl)-3,5-diphenyl-1H-pyrazoles 5 by reaction of secondary amines with the tosylate of 1, are described. Some of the above compounds showed a considerable sedative effect in mice and a remarkable platelet antiaggregating activity in vitro, as well as moderate local anesthetic, analgesic and antiinflammatory activities in mice and rats.

Anesthetics, Local↗
PubMed1990

3,5-Diphenyl-1H-pyrazole derivatives. VII--Esters, 2-dialkylaminoethyl ethers and N-substituted carbamates of 1-(2-hydroxy-3-phenoxypropyl)-3,5-diphenyl-1H-pyrazole with depressant and platelet antiaggregating activities.

The syntheses of 1-(2-hydroxy-3-phenoxypropyl)-3,5-diphenyl-1H-pyrazole 2 by reaction of 1-hydrazino-3-phenoxy-2-propranolol with dibenzoylmethane, of esters 3 and 2-dialkylaminoethyl ethers 4 starting from 2 as sodium salt and acyl chlorides or 2-chloroethyldialkylamines, respectively, as well as of N-aryl carbamates 5 by reaction of 2 with aryl isocyanates, are described. Some of the above compounds showed a considerable sedative effect in mice and a remarkable platelet antiaggregating activity in vitro, as well as moderate local anesthetic, analgesic and antiinflammatory activities in mice and rats.

Anesthetics, Local↗
PubMed1990

omega-Dialkylaminoalkyl ethers of 5-endo-dialkylamino-1,3,3-trimethyl-2-oxabicyclo [2.2.2]octan-6-hydroxyimines with platelet antiaggregating, antiarrhythmic and local anesthetic activities.

The synthesis of 1,3,3-trhimethyl-5-endo-(1-piperidinyl)- and -5-endo-(4-morpholinyl)-2- oxabicyclo [2.2.2]octan-6-hydroxyimine 3 and 4 starting from 5-endo-bromo-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-hydroxyimine+ ++ and excess piperidine or morpholine is described. Compounds 3 and 4 gave a series of omega-dialkylaminoalkyl ethers 5 by reaction as sodium salts with omega-chloroalkyldialkylamines in DMF solution. Some of aminoethers 5 showed in mice an appreciable antiarrhythmic and local anesthetic activity, as well as a platelet antiaggregating activity in vitro comparable to that of acetylsalicylic acid.

Amines↗
PubMed1990

Research on heterocyclic compounds. XXVI. Antiinflammatory and related activities of some 2-phenylimidazo[1,2-b]pyridazines.

Five acidic phenyl derivatives of the imidazo[1,2-b]pyridazine system were subjected to some tests in vivo in order to evaluate their biological activity. Antiinflammatory activity was studied by means of the carrageenin rat paw edema, whereas writhing induced in mice by acetic acid was used to assess analgesic activity. The irritative and ulcerogenic action on the rat gastric mucosa was examined after oral administration of larger doses. The inhibitory activity on platelet malondialdehyde production was studied in vitro. The experimental results are discussed from the point of view of structure-activity relationships and mode of action.

Analgesics↗
PubMed1990

Role of purinergic system in tracheobronchial reactivity of healthy and bronchopathic subjects.

We have investigated the effect of inhaled adenosine on bronchomotor tone in 16 healthy and 24 allergic and non-allergic bronchopathic subjects. We determined the inhaled adenosine dose-response curves after no treatment and after treatment with aminophylline (240 mg in 10 min), reproterol (90 mcg in 2 min) and salbutamol (100 mcg in 2 min) administered intravenously 15 min before adenosine and reproterol (500 mcg) and salbutamol (200 mcg) administered by inhalation from a metered aerosol 30 min before adenosine on separate days. Without prior treatment, inhaled adenosine caused bronchoconstriction in both groups of subjects (normal, and atopic and non-atopic asthmatic ones), but the peripheral airways revealed only a moderate change in normal subjects. Aminophylline caused a greater inhibition of adenosine bronchoconstriction than did reproterol. These results suggest that inhaled adenosine bronchoconstriction involved purinergic transmission and that it is mediated via a P1/Ri (A-1/R1) receptor. Aminophylline is a potent antagonist at purinoceptor level. Reproterol inhibits bronchoconstriction by a mechanism independent of its effect on beta-adrenergic receptors. Because salbutamol, i.e. a beta 2-agonist bronchodilator, did not inhibit adenosine-induced bronchoconstriction (or very nearly so), our results support the view that reproterol antagonizes P1/Ri (A1/R1) tracheobronchial receptors.

Adenosine↗
PubMed1990

Flunarizine in long-term migraine prophylaxis: clinical evidence.

The aim of our study was to evaluate the efficacy of long-term migraine prophylaxis with flunarizine. The efficacy of the drug was evaluated on the basis of the frequency, pain severity and duration of migraine attacks. Frequency, the most modified parameter, was reduced to about half of the pre-treatment level in one to three months time. The condition remained more or less stable from the third treatment month onwards. The results showed remarkable efficacy of long-term prophylaxis with flunarizine, and the response was better in younger patients with a short history of migraine.

Adult↗
PubMed1990

2H-[1]benzothiepino [5,4-b]pyran derivatives with local anesthetic and antiarrhythmic activities.

The synthesis of some N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-[1]benzothiepino [5,4-b]pyran-2-ones by reaction of phenylchloroketene with a series of N,N-disubstituted (E)-4-aminomethylene-3,4-dihydro-1-benzothiepin-5(2H)-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. The 4-methylphenylamino derivative showed a local anesthetic activity in mice superior to that of lidocaine and the 4-morpholino derivative showed an antiarrhythmic activity in rats comparable to that of quinidine.

Anesthetics, Local↗
PubMed1990

2H,5H-[1]benzothiopyrano [4,3-b]pyran derivatives with platelet antiaggregating activity.

The synthesis of some N,N-disubstituted 4-amino-3-phenyl-2H,5H-[1]benzothiopyrano [4,3-b]pyran-2-ones by reaction of phenylchloroketene with a series of N,N-disubstituted 3-aminomethylene-2,3-dihydro-4H-1-benzothiopyran-4-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. Some of these compounds showed a strong platelet antiaggregating activity in vitro, superior to that of acetylsalicylic acid.

Anesthetics, Local↗
PubMed1990

4-Substituted 1-phenyl-1H-indazoles with analgesic, antiinflammatory, antipyretic and local anesthetic activities.

The synthesis of amides 3 and 4 starting from (1-phenyl-1H-indazol-4-yl)acetic and [(1-phenyl-1H-indazol-4-yl)oxy]acetic acids, respectively, as well as of 2-(1-phenyl-1H-indazol-4-yl)ethanamines 5 starting from 3, is described. Moreover, a number of 2-[(1-phenyl-1H-indazol-4-yl)oxy]ethanamines 7 and 3-[(1-phenyl-1H-indazol-4-yl)oxy]propanamines 8 were prepared starting from 1-phenyl-1H-indazol-4-ol. Some compounds 3, 4 and 7 showed an appreciable analgesic activity in mice, whereas compounds 4 were moderately active as antiinflammatory agents in rats. Some compounds 3, 4, 5, 7 and 8 showed also local anesthetic and a weak antipyretic activity in mice and rats, respectively.

Anesthetics, Local↗
PubMed1989

Influence of rat prenatal and postnatal exposure to a non-steroidal anti-inflammatory agent (flunoxaprofen) on cardiovascular function in the progeny.

The present experiments evaluated in rats the effects of prenatal and postnatal exposure to a non-steroidal antiinflammatory agent, flunoxaprofen (5-10 and 20 mg/kg/day by the oral route), on cardiovascular function in the pups. In both conscious and anaesthetized rats pre- and postnatal flunoxaprofen exposure at the 30th and 60th day of age, significantly (P less than .05) induced a decrease of pressor response to carotid-sinus baroreceptor stimulation and to L-noradrenaline (0.1-1 and 5 micrograms/kg iv), and an increase of the hypotensive responses to L-isoprenaline (0.01-0.1 and 1 microgram/kg iv) and acetylcholine (0.01-0.1 and 1 microgram/kg iv). These effects were not observed in rats on the 90th day of age. Moreover, pre- and postnatal flunoxaprofen exposure did not modify systolic arterial blood pressure of plasma levels of catecholamines and acetylcholinesterases. Our results also show that in normotensive rats flunoxaprofen exposure during pregnancy did not affect the body weight, systolic or diastolic blood pressure or heart rate of pregnant rats. It did not affect the length of gestation, number of pups per litter or pup body weight. No macroscopic teratogenic effects were observed.

Acetylcholine↗
PubMed1989

Injection of muscimol into posterior hypothalamus blocks stress-induced tachycardia.

We have previously shown that the physiological and behavioral manifestations of emotional stress are produced when drugs impairing gamma-aminobutyric acid (GABA)-mediated synaptic inhibition are injected into the posterior hypothalamic nucleus in rats [Wible, J.H., Jr., F.C. Luft, and J.A. DiMicco. Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R680-R687, 1988]. The purpose of this study was to assess further the potential role of GABA receptors in this region in the response to stress using muscimol, a GABAA receptor agonist. In six chronically instrumented conscious rats, air stress after vehicle treatment evoked marked and sustained tachycardia (+130 +/- 14 beats/min at +10 min) accompanied by a less dramatic increase in arterial pressure (+14 +/- 3 mmHg). Microinjection of muscimol (10 ng; 88 pmol) at the same posterior hypothalamic site in which GABA blockade causes cardiovascular changes similar to those seen in stress produced a modest depression of cardiovascular function in unstressed animals (-28 +/- 5 beats/min and -6 +/- 3 mmHg). However, similar treatment with muscimol virtually abolished the stress-induced tachycardia in the same rats (+9 +/- 8 beats/min), while having no significant effect on baroreflex-evoked increases in heart rate caused by intravenous infusion of sodium nitroprusside (4 micrograms). These findings support a role for activation of neurons in the posterior nucleus of the hypothalamus in the generation of stress-induced cardiovascular changes and for control of this mechanism by local GABA receptors.

Animals↗
PubMed1989

Evidence of muscarinic receptor subtypes in airway smooth muscle of normal volunteers and of chronic obstructive pulmonary disease patients.

Since there have been only a few studies on muscarinic receptor subtypes in airway smooth muscle, the effect was investigated of pirenzepine on airways of patients with chronic obstructive pulmonary disease (COPD) and the functional responses compared from these patients with those from healthy subjects. Our data demonstrated that the therapy with pirenzepine significantly improved ventilatory function in patients with COPD. The data also suggested that this drug exerts its action on small airways, but not larger airways in normal subjects. It is possible that in healthy human beings pirenzepine produces mild bronchodilation by means of a vagal efferent blockade, while in patients with COPD, it may be effective because it not only decreases the activity of the vagal efferent pathway, but also decreases the sensitivity of vagal sensory endings and causes a vagal afferent blockade.

Atropine↗
PubMed1989

Muscarinic M-1 receptors mediate the bronchial hyperresponsiveness during methacholine inhalation.

Several data suggest that muscarinic M-1 receptors are located on airway smooth muscle of human beings and dogs. Muscarinic M-1 receptors, whose stimulation is associated with enhancement of acetylcholine release, may also be located in the airway parasympathetic ganglia. To determine if postsynaptic muscarinic M-1 receptors mediate airway constriction, the action was compared of pirenzepine, that antagonizes selectively muscarinic M-1 receptors, and atropine, that blocks both muscarinic M-1 and M-2 receptors, on bronchial responses to methacholine inhalation in seven asthmatic patients. Pirenzepine and atropine gave protection against methacholine; however, the degree of protection by pirenzepine was significantly less than that given by atropine. Some inhibitory effect was obtained in all the patients studied after pirenzepine administration, even though some patients were only slight responders. The significant finding of the study is that pirenzepine partially inhibits the bronchospastic response to methacholine. This result suggests that muscarinic receptors on airway smooth muscle are also of the M-1 subtype.

Administration, Inhalation↗
PubMed1989

Pharmacodynamic profile of fenoverine, a novel modulator of smooth muscle motility.

Experimental research has documented that fenoverine is a depressant drug mostly active on the intestinal smooth muscle; however, it is also active on other tissues as well as on the genito-urinary tract. Fenoverine may be considered a synchronizer of smooth muscle effective in modulating the intracellular influx of calcium into the cell and its release from the intracellular pool. Fenoverine causes a reduction of the excitatory junction potential (EJP) in intestinal smooth muscle by stimulating parasympathetic efferent fibres without any change in the inhibitory junction potential (IJP). This also occurs in the presence of atropine. Fenoverine reduces the intracellular Ca2+ concentration by decreasing the calcium gradient across the cell membrane, as well as decreasing the release of Ca2+ from the intestinal pool more intensely than papaverine (but less intensely than nifedipine, verapamil or diltiazem). This phenomenon has been observed in the intestinal smooth muscle and also in the genito-urinary tract.

Animals↗