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R Ceserani

Publications and source records attributed to R Ceserani.

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

Pharmacological activities of the main metabolite of flavoxate 3-methylflavone-8-carboxylic acid.

The pharmacological properties of 3-methylflavone-8-carboxylic acid (MFCA), the main metabolite of flavoxate, have been studied in vitro and in vivo. MFCA did not display antispasmodic activity on isolated organs contractions induced by histamine, acetylcholine or CaCl2, nor did it exhibit significant affinity for the rat brain alpha- and beta-adrenergic, serotoninic, muscarinic, D2, opiate and Ca2+ receptors. However, it showed a remarkable phosphodiesterase (PDE) inhibiting activity. Moreover in vivo studies indicate an interesting activity of MFCA which inhibited the rat urinary bladder voiding contractions, increased bladder volume capacity and decreased micturition pressure in the rat cystometric recordings. The activity of MFCA in the two in vivo experimental models, probably related to cAMP-PDE inhibitory properties, suggests that flavoxate's therapeutical potential might be partially sustained by its main metabolite.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1987

Relationship between the brain levels and the anticonvulsant activity of denzimol after its acute and repeated administration to mice.

The relationship between the brain concentration of denzimol and its anticonvulsant activity was studied in mice after acute and repeated administration (14 days) of this drug to mice. Anticonvulsant activity was assessed against maximal electroshock seizures (MES). When denzimol was administered at 30 mg/kg p.o. to repeatedly treated mice, its brain concentration and anticonvulsant activity were reduced in comparison to non-treated mice and t1/2 beta was significantly changed from 2.10 to 1.53 hr. Tonic hindlimb extension was completely abolished at a brain denzimol concentration higher than 15 mcg/g, whereas the minimum effective brain concentration was between 2-3 mcg/g both in acute and repeatedly treated animals. The brain concentration of denzimol is closely correlated with its anticonvulsant effect both in acute and repeatedly treated animals. Furthermore these findings seem to suggest that the decreased anticonvulsant activity of denzimol, following repeated administrations, might be due to a development of pharmacokinetic tolerance.

Animals↗
PubMed1987

Depression and excitation induced in mice by two geometric isomers of (+)13,14-didehydro-20-methyl-carboprostacyclin, FCE 22177 and FCE 22176. Comparison with effects on blood pressure and platelet aggregation.

Two geometric isomers of a stable derivative of PGI2 (13,14-didehydro-20-methyl-carbo PGI2), FCE 22177 (5E) and FCE 22176 (5Z), have been injected i.v. in mice (5-400 mcg/Kg) to investigate the effects at CNS level (Irwin's test). The synthetic mixture of the two isomers (5E:5Z = 7:3) was also tested. Isomers 5E and 5Z induced opposite effects: 5E (similar to PGI2) was depressive, 5Z induced stimulation. The mixture showed a strong depressive symptomatology. The two isomers and their mixture induced motor incoordination and impaired the performance of mice in the rotarod test (200 mcg/Kg i.v.). Mice were depressed after 5E and mixture; whilst 5Z induced excitation, in accordance with Irwin's test. 5E and 5Z showed analogous effects on mean blood pressure (hypotension) and heart rate (increase) in normotensive rats, but 5E was 7 times more active than 5Z. The two isomers showed analogous inhibitory effect on guinea-pig platelet aggregation in vitro, but 5E was 30 times more active than 5Z. In conclusion, the two geometric isomers have similar effects on blood pressure, heart rate and platelet aggregation, even if differing quantitatively. In contrast, 5E and 5Z have opposite effects at CNS level on motor function and behaviour. The data suggest the presence of two different sites of action for PGI2 in CNS (Ca2+- and adenylate cyclase-linked?). The two geometric isomers, 5E and 5Z, may be useful to study the PGI2 receptor sites in different tissues.

Animals↗
PubMed1987

The influence of a new prostaglandin E2 analogue (FCE 20700) on gastric acid and pepsin secretion in the dog.

The effects of FCE 20700, a new prostaglandin E2 analogue, on gastric acid and pepsin secretion stimulated by different secretagogues were studied in dogs. Intravenous FCE 20700 produced a significant inhibition of total acid output (TAO) induced by pentagastrin or histamine in gastric fistula (GF) dogs. This effect was short-lasting and mainly due to a reduction in the volume of gastric juice with little acid concentration change. TAO and pepsin output stimulated by 2-deoxy-D-glucose were similarly inhibited by intravenous FCE 20700. In dogs chronically fitted with both GF and Heidenhain pouch (HP), intragastric FCE 20700 significantly inhibited TAO stimulated by pentagastrin or histamine from HP, while acid secretion from GF was not significantly affected. It is concluded that FCE 20700 possesses a weak antisecretory activity in dogs. Consequently the antiulcer effects of this prostaglandin derivative seem to be largely independent from its influence on gastric acid and pepsin secretion.

Animals↗
PubMed1986

Pharmacological evaluation of 5-(Z,E)-13,14-didehydro-20-methyl-carboprostacyclin (FCE 22509).

FCE 22509, 5-(Z,E)-13,14-didehydro-20-methyl-carboprostacyclin, a chemically stable prostacyclin (PGI2) derivative, was 3.5 times more potent than PGI2 in relaxing bovine coronary artery in vitro; unlike PGI2, it did not contract bovine coronary vein and it antagonized PGI2-induced contractions of the coronary vein. In vitro smooth muscle (guinea pig ileum and trachea and rat stomach strip) was contracted to a lesser extent than with PGI2. FCE 22509 was about five times less potent than PGI2 in deaggregating platelet clumps formed on rabbit Achilles tendon bathed with heparinized cat blood (ED50 = 7.6 and 1.6 mcg/kg i.v. respectively). In the conscious normotensive and spontaneously hypertensive rat FCE 22509 lowered mean systemic arterial pressure (MSAP) (ED25 = 11.5 and 4.8 mcg/kg i.v.) to a lesser extent than PGI2 (ED25 = 2.1 and 2.34 mcg/kg i.v.) and increased heart rate but not dose-dependently. Orally administered, FCE 22509 likewise reduced MSAP though at high dosages (ED30 = 1.33 and 1.02 mg/kg in normotensive and hypertensive rats). Heart rate (HR) was raised after i.v. and oral treatment but not dose-dependently. In the open-chest anaesthetized dog, FCE 22509, compared with PGI2 at the same three doses, 0.2, 0.4 and 0.8 mcg/kg i.v., lowered MSAP but its hypotensive effect was less pronounced than that of PGI2. Like PGI2, FCE 22509 did not modify HR (though PGI2 showed a tendency to a decrease and FCE 22509 seemed to increase this cardiovascular function) and mean pulmonary arterial pressure (MPAP) and likewise significantly reduced myocardial contractile force. After infusion of PGI2 and FCE 22509 0.2 mcg/kg i.v. for 15 min in the open chest anaesthetized cat, the ex-vivo ADP-induced inhibition of platelet aggregation was the same for both compounds. Unlike PGI2, which reduced MSAP and MPAP, FCE 22509 had no significant lowering effect on MSAP and MPAP.

Animals↗
PubMed1986

Conformational effects on the activity of drugs. 11. Stereostructural models for the direct activation of the alpha- and beta-adrenergic receptor.

Two kinds of cyclic analogues of norepinephrine (NE, 7) and isoprenaline (ISO, 8), in which the C(1)-C(2) side chain of these amino alcohols is incorporated in its preferred conformation in the ring of the 2-(3,4-dihydroxyphenyl)-morpholines 9 and 10 (2-DPMs) and in the ring of the 3-(3,4-dihydroxyphenyl)-3-piperidinols 11 and 12 (3-DPPs), respectively, were synthesized and assayed for their adrenergic activity on various isolated preparations. The 2-DPMs and the 3-DPPs showed an alpha- and beta-agonist activity comparable to that of NE and ISO and to that of the trans-2-amino-5,6-dihydroxytetrahydronaphthalen-1-ols 13 and 14 (2-ADTNs), which represent another kind of semirigid analogue of NE and ISO. Through a comparison of the stereo structures of the compounds examined and of their pharmacological properties, it was possible to suggest a spatial situation in which the pharmacophoric groups of the adrenergic drugs examined (aryl moiety, amine nitrogen, and alcoholic or ethereal benzylic oxygen) should interact at the receptor site. This spatial situation corresponds to the one found in the preferred conformation of NE and ISO. It was also possible to construct two theoretical three-dimensional molecular models that provide information about steric requirements for the direct activation of alpha- and beta-adrenoceptors, respectively.

Animals↗
PubMed1986

Synthesis and antiulcer activity of (E)-5-[2-(3-pyridyl)ethenyl]-1H,7H-pyrazolo [1,5-a]pyrimidine-7-ones.

A series of (E)-5-[2-(3-pyridyl)ethenyl]-1H,7H-pyrazolo-[1,5-a]pyrimidine-7-ones were synthesized and evaluated for the inhibition of stress-induced gastric ulcers in the rat after oral administration. Several molecules were found to be very active. The particularly interesting compound (E)-1-(3-chlorophenyl)-5-[2-(3-pyridyl)ethenyl]-1H,7H-pyrazolo[1,5-a]- pyrimidine-7-one was chosen for wider pharmacological investigation.

Animals↗
PubMed1985

Hypotensive effect in the rat after oral prostacyclin (PGI2).

PGI2 dose dependently lowers mean systemic arterial pressure in conscious normotensive and spontaneously hypertensive rats after oral administration. The ED30 was respectively 0.79 and 0.63 mg/kg. Heart rate was not significantly modified. The hypotensive effect appears to be due to PGI2 itself and not to its metabolite 6-keto-PGF1 alpha which, administered at 2 mg/kg p.o., did not modify blood pressure.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Carbon tetrachloride-induced pharmacokinetic changes of diazepam in rats are reduced by a stable analogue of prostaglandin E2 : FCE 20700.

Rats, given CC14 (6670 mg/Kg, sc), exhibited a significant increase in SGPT (425.7 +/- 51.3 mU/ml), together with impaired pharmacokinetics of intravenous diazepam (t beta 1/2: 53.87 h; AUC: 101.05 micrograms/ml/h) when compared with saline treated animal (SGPT: 33.6 +/- 3.8 mU/ml; t beta 1/2: 2.087 h; AUC: 1.37 micrograms/ml/h). FCE 20700 (5 micrograms/ml, sc) did not change, by itself, either SGPT or diazepam pharmacokinetic parameters, but significantly antagonized the changes induced by CC14 (SGPT: 45.3 +/- 5.3 mU/ml; t beta 1/2: 0.167 h; AUC: 2.426 micrograms/ml/h). Further support to this cytoprotective effects was given by histological examination of the livers. Data indicate that this new prostaglandin E2 derivative might be useful in patients with liver failure.

Alanine Transaminase↗
PubMed1984

Cytoprotective and antisecretory effects of 11-deoxy-13,14-didehydro-16(s)-methyl PGE2 methylester (FCE 20700).

A new, chemically stable analogue of PGE2, 11-deoxy-13,14-didehydro-16(S)-methyl PGE2 methylester (FCE 20700) was studied for the prevention of different gastrointestinal ulcers and for the inhibition of basal gastric acid secretion in the rat. The diarrhoea-inducing activity was also investigated. FCE 20700 was more potent than PGE2 in the prevention of stress-induced gastric ulcers (ED50 = 262 and 787 mcg/kg) and indomethacin-induced intestinal ulcers (ED50 = 557 and 4569 mcg/kg), and showed the same potency as PGE2 in the prevention of ethanol (ED50 = 9.2 and 14.8 mcg/kg) and indomethacin-induced gastric ulcers (ED50 = 37.8 and 22.3 mcg/kg). FCE 20700 weakly affects gastric acid secretion with an ED50 of 2385 mcg/kg, showing clear separation of antisecretory activity and gastric antiulcer potency. FCE 20700 does not induce diarrhoea in rats at doses up to 6.25 mg/kg, 10 to 600 times the effective antiulcer doses.

Animals↗
PubMed1984

New derivatives of pyrrolo and pyrido[2,1-b] quinazoline as antiulcer agents.

A series of 3-benzylidene-1,2,3,9-tetrahydro-9-oxopyrrolo-[2,1-b] quinazolinecarboxylic acids and 6-benzylidene-6,7,8,9-tetrahydro-11-oxo-11H-pyrido[2,1-b] quinazolinecarboxylic acid was synthesized and evaluated for their antiulcer activity by the test of inhibition of restraint ulcers in the rat, and for gastric antisecretory activity using the technique of Shay. Some compounds appear potentially useful for therapeutic application.

Animals↗
PubMed1983

A comparative study of PGI2 and two analogues (FCE 21292 and FCE 21258) in vitro and in vivo.

Two analogues of PGI2, FCE 21258 (5E-13,14-didehydro-carboprostacyclin) and FCE 21292 (5E-13,14-didehydro-20-methyl-carboprostacyclin) have been evaluated in comparison with PGI2 in different in vitro and in vivo screening tests. The rank order of potency was PGI2 greater than FCE 21292 greater than FCE 21258 in the following tests: potentiation of bradykinin-induced increased plasma protein extravasation in the guinea pig skin, inhibition of guinea pig platelet aggregation in vivo where the duration of action of FCE 21292 was longer than that of PGI2, lowering of mean systemic arterial pressure in conscious normotensive and spontaneously hypertensive rats and inhibition of rabbit platelet aggregation in vitro. In the relaxation of bovine coronary artery in vitro the rank order of potency was FCE 21292 greater than PGI2 greater than FCE 21258.

Animals↗
PubMed1983

FCE 20700, a cytoprotective PGE2 derivative, does not interfere with the antiinflammatory activity of indomethacin.

A study was made of the interaction between FCE 20700 (11-deoxy-13,14-didehydro-16(S)-methyl-PGE2 methylester) at a fixed dose of 250 mcg/kg and the ulcerogenic and antiinflammatory effect of indomethacin (I) on rat carrageenin paw edema. The combination tested showed the same antiinflammatory effect as I alone: potency ratio FCE 20700 + I/I was 1.03, demonstrating the lack of interaction between the two compounds. Moreover the gastric lesions in FCE 20700 + I treated rats were markedly reduced, allowing the dosage of I to be increased by about three times without increasing its ulcerogenic effect.

Animals↗
PubMed1981

Azaprostaglandin analogues. Synthesis and biological properties of 11-azaprostaglandin derivatives.

New nitrogen analogues of prostaglandins (11, 11a, 12, and 12a) have been synthesized starting from a 4,5-disubstituted 2-pyrrolidinone nucleus (5 and 5a) containing one side chain and a suitable functionality for elaborating the second one. These analogues had no better activity than natural prostaglandins in vitro [guinea pig ileum and trachea, rat stomach fundus strip, uterus and portal vein, ADP-induced guinea pig platelet-rich plasma (PRP) aggregation]. They similarly lacked any interesting activity in vivo [anesthetized rat blood pressure, stress, and acetylsalycilic acid (ASA) induced gastric lesions in rat].

Animals↗
PubMed1980

dl-9a-Deoxy-9a-methylene-PGI2 (a stable prostacyclin derivative): preliminary pharmacological data.

Carboprostacyclin (dl-9a-deoxy-9a-methylene-PGI2), a new stable PGI2-analogue, has been studied in vitro and in vivo. This analogue relaxes bovine coronary artery (potency ratio to PGI2 = 0.17), inhibits human PRP aggregation induced by ADP (IC50 = 12.5 nM2), deaggregates platelet clumps in cat heparinized blood (ED50 = 10.4 microgram/kg) and raises cAMP content in human PRP, but is less potent than PGI2. It is less potent (about 30 times) than PGI2 in lowering blood pressure in anaesthetized rats, inhibits basal gastric secretion in the rat and is 8 and 6 times less potent than PGE2 in protecting rat gastric mucosa from the lesions induced by stress and ASA, respectively, and about half as potent as PGE2 in protecting intestinal mucosa from damage by indomethacin.

Animals↗