Search PubMed⌕ Search

Biomedical subjects

A Filippelli

Publications and source records attributed to A Filippelli.

At least 55 records · Page 3Linked to original sources
PubMed1994

O-[omega-(Dialkylamino)alkyl]oximes of (+)-1,7,7-trimethylbicyclo [2.2.1]heptan-2-one with hypotensive, antiinflammatory, analgesic, local anesthetic and other activities.

The synthesis of (+)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one O-[omega-(dialkylamino)alkyl]oximes by reaction of (+)-camphoroxime sodium salt with a series of omega-(chloroalkyl)dialkylamines in DMF solution is described. Some of the above compounds showed strong hypotensive, antiinflammatory, analgesic and local anesthetic activity in rats and mice, as well as moderate antiarrhythmic, antipyretic and in vitro platelet antiaggregating activity.

Analgesics↗
PubMed1994

Effects of the intracerebroventricular administration of ketamine on centrogenic arrhythmias in anesthetized rats.

In urethane anesthetized rats the icv (lateral cerebral ventricle) administration of ketamine, at the highest utilized doses, induced bradypnea and sinus bradycardia in spontaneously breathing rats. Moreover, it partially antagonized the arrhythmogenic activities of sodium glutamate and sodium aspartate, as well as desipramine and ouabain. From these results, we conclude that ketamine had an inhibitory effect on the centrogenic arrhythmias not only acting at the level of NMDA subtype receptor, but also at beta 1 adrenergic central receptors. Moreover at high doses, ketamine can also induce centrogenic arrhythmias in spontaneously breathing rats.

Anesthesia↗
PubMed1994

O-(2-dialkylaminoethyl)oximes of 5-(arylmethylene)-1,3,3-trimethyl-2-oxabicyclo [2.2.2]octan-6-ones with hypotensive, antiarrhythmic and other activities.

The synthesis of some O-(2-dialkylaminoethyl)oximes of 5-[(4-methoxy- or 4-methylthiophenyl)methylene]-1,3,3-trimethyl-2-oxabicyclo[2.2.2] octan-6-ones 5 by reaction of the corresponding oximes as sodium salts with the appropriate 2-chloroethyldialkylamine in dry ethanol solution is described. Some aminoethers 5 showed appreciable hypotensive and antiarrhythmic activities in rats, as well as a weak platelet antiaggregating activity in vitro and a moderate infiltration anesthesia in mice.

Anesthetics, Local↗
PubMed1994

Docosahexaenoic acid and signaling pathways in rabbit colon.

The effects of one of the main components of fish oil, docosahexaenoic acid (DHA), on prostaglandin (PG) and Ca2+ signaling pathways were examined in intact mucosa and freshly isolated crypt cells of rabbit descending colon. Preincubation of serosal mucosa for 20 min with 1 microM DHA fully suppressed the short-circuit and transepithelial conductance increase induced by serosal addition of 10 microM arachidonic acid (AA). DHA at 1 microM also prevented the Cl- secretion promoted by 10 microM AA, as estimated by unidirectional 36Cl flux measurements (net flux = 0.68 +/- 0.30 versus -1.91 +/- 0.20 microEq/hr/cm2, four experiments, p < 0.001), whereas it did not affect the electrophysiological and ion flux responses to PGE2. Addition of 1 microM DHA to the serosal side of the mucosa also inhibited the PG cascade activation elicited by AA (PG synthesis and second messenger cAMP increase). In vitro assays of colonic cyclooxygenase activity showed that 1 microM DHA inhibited (with a 20-min lag) cyclooxygenase activity to the same extent as 5 microM indomethacin (approximately 82% and 80%, respectively). DHA also affected the Ca2+ signaling pathway; in isolated crypt cells, the cytosolic free Ca2+ concentration ([Ca2+]i) dropped by 49 +/- 7.6% (mean +/- standard error, six experiments) after incubation with 1 microM DHA. The sustained phase of the [Ca2+]i response to 500 nM concentrations of the intracellular Ca(2+)-ATPase inhibitor thapsigargin was also inhibited within 150 sec upon 1 microM DHA addition (141 +/- 5.8 versus 243 +/- 8.2 nM [Ca2+]i mean +/- standard error, eight experiments, p < 0.01). The [Ca2+]i-lowering effect of DHA, which was not achieved by incubation with other free fatty acids, was not prevented by removal of Na+ from the incubation medium (-46 +/- 4.3% versus -47 +/- 3.8%, mean +/- standard error, four experiments), nor it was mediated by cAMP-, protein kinase C-, or calmodulin-dependent mechanisms. The incubation of highly purified basolateral membranes of crypt cells with 1 microM DHA for 1 min produced a 5-fold increase (IC50 = 0.25 microM) in the plasma membrane Ca(2+)-ATPase activity (34.3 +/- 2.73 versus 6.02 +/- 0.50 nmol/mg of protein/min, mean +/- standard error, four experiments, p < 0.0001), thus indicating that the DHA effects on the Ca2+ pathway were mediated mainly by an increase in plasma membrane Ca2+ pump activity. These findings suggest that DHA is a powerful modulator of the cellular response to activation of PG and Ca2+ signaling pathways.

Animals↗
PubMed1994

[The therapeutic prospects of ischemic cardiopathy].

Having thoroughly reviewed the risk factors and pathophysiologic features of ischemic heart disease, the authors describe therapeutic protocols at present in use and take stock of the perspectives opened by new drugs with different kinetic and dynamic and more advanced properties compared to those at present in use.

Cardiovascular Agents↗
PubMed1993

Involvement of periaqueductal gray area NMDA receptors in endothelin-induced behavioural effects.

We investigated the behavioural effects induced by endothelin-1 injected into the lateral-caudal periaqueductal gray matter of freely moving rats. Endothelin-1 induced a dose-dependent longitudinal rolling of the body (barrel rolling) which was prevented by D,L-2-amino-5-phosphonovalerate (2-APV), an N-methyl-D-aspartate (NMDA) receptor antagonist, but not by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antagonist. This effect, not reproducible with NMDA alone, indicates that the activation of the NMDA receptors in the periaqueductal gray area may be a necessary, but not sufficient, step for the triggering of endothelin-1-induced barrel-rolling behaviour.

2-Amino-5-phosphonovalerate↗
PubMed1993

N-acyl-4,7,7-trimethyl-N-phenyl-3-(1-piperidinyl or dimethylamino)bicyclo[2.2.1]hept-2-ene-2-carbothioamides with platelet antiaggregating and other activities.

A series of N-acyl-4,7,7-trimethyl-N-phenyl-3-(1-piperidinyl or dimethylamino)bicyclo[2.2.1]hept-2-ene-2-carbothioamides was prepared in excellent yields by reaction of 4,7,7-trimethyl-N-phenyl-3-(1-piperidinyl or dimethylamino)bicyclo[2.2.1]hept-2-ene-2-carbothioamides with a number of aromatic or heterocyclic acyl chlorides in dry pyridine solution and in the presence of sodium hydride. Some of the above compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid; moreover, some compounds exhibited moderate analgesic, antiinflammatory and hypotensive activities in mice or rats.

Acetylcholine↗
PubMed1993

2H-1-benzopyran derivatives with platelet antiaggregating and other activities.

The synthesis of some N,N-disubstituted 4-amino-5,6,7,8-tetrahydro-3,6- diphenyl-2H-1-benzopyran-2-ones by reaction of phenylchloroketene with a series of N,N-disubstituted 2-aminomethylene-4-phenylcyclohexanones, followed by dehydrochlorination in situ of the primary adducts with DBN, is described. Some compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid and an appreciable antiarrhythmic activity, as well as weak anti-inflammatory and local anesthetic activities in rats and mice.

Aconitine↗
PubMed1993

3,5-diphenyl-1H-pyrazole derivatives. XI. N-aryl-5(3)-phenyl-4-(3,5- diphenyl-1-pyrazolyl)-3(5)-pyrazole amines, 5-substituted 4,5-dihydro-3-phenyl-4-(3,5-diphenyl-1-pyrazolyl)-1H-pyrazoles and 2,6-disubstituted 1,6-dihydro-4- phenyl-5-(3,5-diphenyl-1-pyrazolyl)pyrimidines with antipyretic, antiinflammatory and other activities.

The synthesis of N-aryl-5(3)-phenyl-4-(3,5-diphenyl-1-pyrazolyl)-3(5)- pyrazoleamines 3 by reaction of some N-aryl-3-oxo-3-phenyl-2-(3,5-diphenyl-1- pyrazolyl)propanecarbothioamides with hydrazine is described. Also prepared were 4,5-dihydro-3-phenyl-4-(3,5-diphenyl-1-pyrazolyl)-1H-pyrazoles 6 and 1,6-dihydro-4-phenyl-5-(3,5-diphenyl-1-pyrazolyl)pyrimidines 7 by reaction of 1-phenyl-2-(3,5-diphenyl-1-pyrazolyl)-2-buten-1-one with hydrazine or guanidine and benzamidine, respectively. Some compounds 3, 6 and 7 showed remarkable antipyretic, antiinflammatory and in vitro platelet antiaggregating activities, as well as weak analgesic, antiarrhythmic, hypotensive and local anesthetic activities in rats and mice.

Anesthetics, Local↗
PubMed1992

4H-thieno[3,4-c]pyrazole derivatives with antiinflammatory, analgesic, antipyretic and platelet antiaggregating activities.

The synthesis of a series of 1-aryl-1,6-dihydro-4H-thieno[3,4-c]pyrazol-4-ones by cyclization of 3-[(2-arylhydrazino)methylene]thiophene-2,4(3H,5H)-diones, prepared by reacting 3-dimethylaminomethylenethiophene-2,4(3H,5H)-dione with arylhydrazines, is described. The 4-fluorophenyl derivative showed remarkable analgesic, antiinflammatory and antipyretic activities in mice or rats, as well as a platelet antiaggregating activity in vitro comparable to that of acetylsalicylic acid.

Acetates↗
PubMed1992

Effects of flunoxaprofen, a non-steroidal anti-inflammatory agent, on the cardiovascular system.

The effects of flunoxaprofen (FL) were investigated using anesthetized normotensive and spontaneously hypertensive (SHR) young and old rats. The animals were divided into two groups. One group received a non-steroidal anti-inflammatory agent at doses significantly inhibiting prostaglandin (PG)-cyclooxygenase; the other received no non-steroidal anti-inflammatory drugs. Oral pretreatment of anesthetized rats with flunoxaprofen (6.6, 11.5, and 19.9 mg/kg/day in the feed for 560 days) significantly increased the following responses: occlusion of the common carotid arteries, and reactivity to L-noradrenaline (NA) (i.v.), and angiotensin II (Ang) (i.v.). Pressor responses also increased in normotensive and in SHR rats treated with FL (20 mg/kg/day for seven days). The effects were more intense in the SHR rats. Moreover, oral pretreatment of normotensive rats with FL (20 mg/kg/day for seven days) partially yet significantly reduced the antihypertensive activity of etozolin (ET), a diuretic and antihypertensive drug. Our data confirm the important role of prostaglandins in the regulation of the cardiovascular system, and an increase in arachidonic acid metabolite biosynthesis with vasodilatory effects being part of the mechanism of action of some antihypertensive drugs.

Administration, Oral↗
PubMed1991

Cardiovascular and respiratory effects of dermorphin in rats.

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.

Analgesics, Opioid↗
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↗
PubMed1989

Interference of prenatal and postnatal exposure to Ca2+-antagonist agents on rat functional development of vascular system.

Exposure to drugs during pregnancy can alter functional development of the vascular system. The present investigation was carried out in order to evaluate the effects of prenatal and postnatal exposure to Ca2+-antagonist (diltiazem, verapamil, and nimodipine) drugs on the development of rat vasomotor reactivity. Studies were carried out on pregnant female albino rats exposed from the first day of pregnancy until weaning to diltiazem and verapamil (6 and 24 mg/kg in their drinking water ad libitum) and nimodipine (3 and 12 mg/kg in their food ad libitum). After weaning, pups were exposed until the 60th day of age to the same treatment as their mothers were. Afterwards, pups from the 60th to 90th day of age were fed with a normal diet. In 30-, 60-, and 90-day-old conscious and anaesthetized pups, we evaluated the following: 1) systolic arterial blood pressure; 2) vasomotor responses elicited by various agents: L-noradrenaline (0.1, 1, and 5 micrograms/kg IV), L-isoprenaline (0.01, 0.1, and 1 micrograms/kg IV), and acetylcholine (0.01, 0.1, and 1 micrograms/kg IV) and by sinus-carotid baroreceptor stimulation; and 3) catecholamine, acetylcholinesterase, and adenosinase plasma levels. Prenatal and postnatal exposure to Ca2+-antagonist drugs significantly (P less than .05) decreased the pressor response to sinus-carotid baroreceptor stimulation and to L-noradrenaline and increased the hypotensive responses to L-isoprenaline and acetylcholine. Moreover, this type of treatment, although it induced a significant (P less than .05) decrease of catecholamine plasma levels, did not modify the acetylcholinesterase and adenosinase plasma levels in 30- and 60-day-old rats. On the 90th day of age, the evaluated parameters were not different from those of control rats. Our results showed that exposure to Ca2+ antagonists during pregnancy and the postnatal period may alter the functional development of rat vasomotor reactivity.

Acetylcholinesterase↗
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↗