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E Poggesi

Publications and source records attributed to E Poggesi.

29 records · Page 2Linked to original sources
PubMed1995

The alpha 1d-adrenoceptor subtype is involved in the noradrenaline-induced contractions of rat aorta.

The pA2 value of several alpha 1-adrenoceptor antagonists on noradrenaline-induced contractions of rat aorta, and their affinity for the cloned alpha 1a-, alpha 1b- and alpha 1d-adrenoceptor subtypes were evaluated. Selective or moderately selective alpha 1d-, partially selective alpha 1b-, selective alpha 1a- and non subtype-selective alpha 1-adrenoceptors antagonists were included in the study. The potency of these compounds on rat aorta was well correlated with the affinity observed for the alpha 1d-adrenoceptor subtype. A poor correlation was found for the alpha 1b- and alpha 1a-subtypes. These results suggest that the alpha 1d-subtype plays a determining role in rat aorta contractions induced by noradrenaline.

Adrenergic alpha-Antagonists↗
PubMed1995

Mediation of noradrenaline-induced contractions of rat aorta by the alpha 1B-adrenoceptor subtype.

1. The subtypes of alpha 1-adrenoceptor mediating contractions to exogenous noradrenaline (NA) in rat aorta have been examined in both biochemical and functional studies. 2. Incubation of rat aortic membranes with the irreversible alpha 1B-adrenoceptor antagonist, chloroethylclonidine (CEC: 10 microM) did not change the KD of [3H]-prazosin binding in comparison to untreated membranes, but reduced by 88% the total number of binding sites (Bmax). 3. Contractions of rat aortic strips to NA after CEC (50 microM for 30 min) incubation followed by repetitive washing, showed a marked shift in the potency of NA and a partial reduction in the maximum response. The residual contractions to NA after CEC incubation were not affected by prazosin (10 nM). 4. The competitive antagonists prazosin, terazosin, (R)-YM-12617, phentolamine, 5-methylurapidil and spiperone inhibited contractions to NA with estimated pA2 values of 9.85, 8.54, 9.34, 7.71, 7.64 and 8.41, respectively. 5. The affinity of the same antagonists for the alpha 1A- and alpha 1B- adrenoceptors was evaluated by utilizing membranes from rat hippocampus pretreated with CEC, and rat liver, respectively. 5-Methylurapidil and phentolamine were confirmed as selective for the alpha 1A-adrenoceptors, whereas spiperone was alpha 1B-selective. 6. A significant correlation was found between the pA2 values of the alpha 1-adrenoceptor antagonists tested and their affinity for the alpha 1B-adrenoceptor subtype, but not for the alpha 1A-subtype. 7. In conclusion, these findings indicate that in rat aorta most of the contraction is mediated by alpha 1B-adrenoceptors, and that the potency (pA2) of an antagonist in this tissue should be related to its antagonistic effect on this subtype of the alpha 1-adrenoceptor population.

Adrenergic alpha-Antagonists↗
PubMed1993

Characterization of alpha 1-adrenoceptor subtypes in prostate and prostatic urethra of rat, rabbit, dog and man.

The alpha 1-adrenoceptor subtypes present in the smooth muscle of urethra and prostate of different animal species, including man, were characterized by using receptor binding techniques. In prostatic urethra and prostate membranes, [3H]prazosin labelled a single population of alpha 1-adrenoceptors (Hill coefficient not different from unity) with a high affinity in the range 0.21-0.51 nM. The number of specific [3H]prazosin binding sites was partially affected by chloroethylclonidine only in human and rat prostate membranes, whereas this agent proved practically devoid of activity in rabbit and dog prostate membranes as well as in the prostatic urethra membranes of all the animal species examined. These findings indicate that in prostatic and urethral membranes the alpha 1-adrenoceptors mainly belong to the alpha 1A subtype. The binding results were confirmed by in vitro functional studies on noradrenaline-induced contractions of rabbit and dog urethral preparations. The agonist-induced contractions were practically unaffected by preincubation of both tissues with chloroethylclonidine, but were sensitive to nifedipine. We found, moreover, a good correlation between the potency of different selective and non-selective alpha 1-adrenoceptor antagonists (WB-4101, 5-methylurapidil, phentolamine, spiperone, prazosin and urapidil) tested against the noradrenaline-induced contractions of rabbit urethra and their affinity for the alpha 1A-adrenoceptor subtype, no correlation with the affinity for the alpha 1B subtype, and a lower correlation with the affinity for the alpha 1C-adrenoceptor subtype.

Adrenergic alpha-Antagonists↗
PubMed1993

Affinity of different alpha 1-agonists and antagonists for the alpha 1-adrenoceptors of rabbit and rat liver membranes.

In membranes prepared from rabbit liver, competition with [3H]prazosin by different alpha 1-agonists and antagonists revealed different affinities in comparison to the results obtained on rat liver membranes, and showed a good correlation with the affinity of the same compounds for the cloned alpha 1c-adrenoceptor subtype. The potencies observed on rat liver membranes were well correlated with the affinity observed for the cloned alpha 1b-adrenoceptors. These results confirm that rabbit and rat liver membranes preparations can be utilized to evaluate the affinity of compounds for these alpha 1-adrenergic subtypes.

Adrenergic alpha-Agonists↗
PubMed1993

Effects of terflavoxate on stimulated contractions of urinary bladder in vitro.

The antispasmodic activity of terflavoxate (CAS 86433-39-8), a flavone derivative with spasmolytic properties on the urinary tract, has been studied in vitro, in comparison to the most common drugs utilized in the therapy of overactive detrusor, namely flavoxate, oxybutynin, and terodiline. Terflavoxate showed affinity for bladder (and brain) muscarinic receptors at micromolar level, however, its activity on carbachol-induced contractions of rat bladder was clearly non competitive, indicating that the compound is devoid of functional antimuscarinic property. Moreover, the observation that unlike antimuscarinic drugs, terflavoxate inhibited by more than 50% field stimulation-induced contractions of rabbit bladder strips, indicates that mechanisms other than the anticholinergic one should be responsible for its smooth muscle relaxant properties. Terflavoxate, flavoxate, oxybutynin, and terodiline were equally effective in inhibiting the two components of K(+)-induced contractions, while nifedipine and nicardipine were more potent than the other compounds, and more effective in inhibiting tonic than phasic contractions. In addition, while nifedipine and nicardipine antagonized in a competitive manner calcium-induced contractions of potassium-depolarized bladder strips, the other spasmolytics behaved as mixed antagonists. Differences in calcium antagonistic properties between nifedipine and nicardipine on one side, and terflavoxate on the other, are further demonstrated by the data on binding experiments. Nevertheless, present results suggest that Ca(++)-antagonistic effects are mainly responsible for terflavoxate smooth muscle relaxant properties.

Animals↗
PubMed1988

Reduction of normal food intake in rats and dogs and inhibition of experimentally induced hyperphagia in rats by CM 57373 and fenfluramine.

The anorectic effect of CM 57373 in dogs and in rats food-deprived or with experimentally induced hyperphagia (cafeteria-diet hyperphagia and insulin hyperphagia) was compared to the effect of serotoninergic anorectic drug dl-fenfluramine. CM 57373 and dl-fenfluramine administered orally caused a dose-related reduction of food consumption by food-deprived rats (ID50 = 7.4 mg/kg and 2.5 mg/kg respectively). The oral ID50 in dogs was 2.4 mg/kg for CM 57373 and 1.1 mg/kg for dl-fenfluramine. This animal species tolerated CM 57373 better than dl-fenfluramine. The latter induced mydriasis, dyskinesia and reduced spontaneous activity. The anorectic effects of CM 57373 and dl-fenfluramine in cafeteria-diet hyperphagic rats were comparable. Tolerance to the anorectic effect developed in rats treated with both CM 57373 and dl-fenfluramine although tolerance was initially less pronounced with CM 57373 than dl-fenfluramine. The brain serotonin levels of cafeteria-fed rats were unchanged by CM 57373 throughout treatment whereas dl-fenfluramine decreased the monoamine levels starting from the 8th day. Both drugs reduced 5-hydroxyindolacetic acid levels. CM 57373 (7.4 mg/kg p.o.) and dl-fenfluramine (2.5 mg/kg p.o.) markedly reduced the overeating caused by insulin injection. These results indicate that CM 57373 shows several characteristics of drugs that act via serotonin to depress food intake in various animal species.

Animals↗
PubMed1980

Pharmacological activities of clobazam and diazepam in the rat: relation to drug brain levels.

Brain distribution and various pharmacological effects of clobazam and diazepam were studied in rats. When given at 10 mg/kg i.p. the compounds reached peak brain levels 15 min after injection, and showed similar half lives. At peak time brain levels were proportional to the dose administered. Very little of the N-desmethylmetabolite of each compound was found in the brain. Clobazam was less effective than diazepam in protecting rats from pentetrazol convulsions. Disrupting rota-rod performance and increasing punished responses in a "conflict" test, the relative potencies ranging from 4 to 8 in the various tests. The results are discussed in relation to the importance of animal species selection for predicting favourable therapeutic effects in humans.

Animals↗
PubMed1979

The roles of brain noradrenaline and dopamine in the anorectic activity of diethylpropion in rats: a comparison with d-amphetamine.

The anorectic activity of diethylpropion and d-amphetamine was studied in rats subjected to various treatments known to affect brain monoamines. The effect of diethylpropion, like that of d-amphetamine, was completely prevented by a lesion of the ventral noradrenergic bundle, which selectively decreases brain noradrenaline, but was not significantly modified in desipramine pretreated rats by an intraventricular injection of 6-hydroxydopamine, a condition decreasing only dopamine. Pretreatment with penfluridol significantly reduced the effect of d-amphetamine but not that of diethylpropion. A non-significant reduction of drug effect was found with alpha-methyl-p-tyrosine. Lesion of the nucleus medianus raphe, which destroys central serotonin neurons, or treatment with methergoline, a central serotonin antagonist, caused no changes in the effects of both compounds. The findings show that integrity of central noradrenergic neurons is an important condition for diethylpropion and d-amphetamine to exert their anorectic effect. Dopamine does not seem to play any role in the effect of diethylpropion but might contribute to that of d-amphetamine. The data are against any involvement of brain serotonin in diethylpropion anorexia.

Animals↗
PubMedDate not supplied

Effects of some antidepressants on the volume-induced reflex contractions of the rat urinary bladder: lack of correlation with muscarinic receptors affinity.

It has been suggested that tricyclic antidepressants such as imipramine, might exert their anti-enuretic action by a blockade of muscarinic receptors in the detrusor muscle of the urinary bladder. We have therefore investigated the effects of two tricyclic (imipramine and nortriptyline) and three atypical (citalopram, amineptine and mianserin) antidepressants on the micturition reflex and muscarinic receptors in rats. The micturition reflex pathway was monitored indirectly by recording the rhythmic intravesical pressure waves which occurred when the bladder was distended and maintained under constant saline-volume. The activity of the antidepressants was correlated to their potencies as antagonists of [3H]QNB binding to rat brain (mainly M1 receptors) and bladder (mainly M2 receptors) membranes, as well as antagonists of carbachol-induced contractions of rat bladder strips. Only imipramine and citalopram dose dependently inhibited the voiding contractions, whereas nortriptyline, imipramine and mianserin (in order of potency) were active both in binding studies and as competitive antagonists of carbachol-induced bladder contractions, but were inactive in inhibiting the micturition reflex. The present data seem to suggest that affinities for muscarinic receptors are unrelated to the inhibition of micturition reflex.

Animals↗