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M O Carruba

Publications and source records attributed to M O Carruba.

89 records · Page 5Linked to original sources
PubMed1979

Evidence for a receptor supersensitivity following impairment of central serotoninergic activity in the rabbit.

In order to investigate whether a chronic impairment of neuronal serotoninergic transmission in the CNS could result in a receptor supersensitivity, rabbits were pretreated either with 5,6-dihydroxytryptamine (5,6-DHT) or p-chlorophenylalanine (PCPA) and then tested for their hyperthermic response to serotoninergic agonists. A previous (10 days before) intracerebroventricular injection of 5,6-DHT (75 microgram into each cerebral ventricle) significantly potentiated the increase in body temperature induced either by quipazine (1 mg/kg i.v.) or by 5-hydroxytryptophan (5-HTP 2 mg/kg i.v.) in combination with a MAO inhibitor (phenylethylhydrazine 10 mg/kg i.v. 16 h before). Pretreatment with PCPA (100 mg/kg s.c. four times on alternate days, the last dose 48 h before the experiment) also enhanced the hyperthermic effect of quipazine, whereas it inhibited the hyperthermic response to 5-HTP plus MAO inhibitor. These results suggest the existence of a receptor supersensitivity following prolonged blockade of serotoninergic neuronal transmission in the CNS.

5,6-Dihydroxytryptamine↗
PubMed1978

Effect of central nervous system-acting drugs after selective destruction by neurotoxins of 5-hydroxytryptamine fibers in the brain.

Some behavioral effects of CNS-acting drugs have been studied in two animal species after functional impairment of central serotonergic activity. In rabbits, pretreatment with p-CPA or with 5,6-DHT counteracted the hyperthermia induced by d-amphetamine or apomorphine; the same pretreatments were ineffective in modifying pyrogen-induced fever. These data indicate a modulatory role of the 5-HT system in the hyperthermic response to dopaminergic agonists, such as d-amphetamine and apomorphine, and rule out 5-HT involvement in the hyperpyrexia induced by pyrogen. A previous intraventricular injection of 5,6-DHT significantly potentiated the increase in body temperature induced by 5-HTP in combination with a MAO inhibitor. Pretreatment with p-CPA, instead, strongly inhibited the hyperthermic response to 5-HTP. In unanesthetized fowl, at the time of the most dramatic degenerative signs of indoleaminergic neurons induced by 5,6-DHT, as documented by histofluorescence pictures, intraventricular infusion of 5-HT induced more intense behavioral, electrocortical, and body temperature modifications than in control animals. These results suggest the existence of receptor supersensitivity after 5-HT nerve ending degeneration but not after brain 5-HT depletion. The hyperthermic effect of a presynaptically acting drug, fenfluramine, was counteracted in rabbits and in fowl pretreated with either p-CPA or 5,6-DHT. Since identical behavioral, electrocortical, and body temperature effects have been observed after 5-HT or 5,6-DHT infusion into the third ventricle of fowl, it may be concluded that 5,6-DHT behaves also as a central 5-HT receptor agonist.

5-Hydroxytryptophan↗
PubMed1977

Effects of mazindol and d-fenfluramine of 5-hydroxytryptamine uptake, storage and metabolism in blood platelets.

Mazindol induced a dose-related inhibition of the uptake of labelled 5-hydroxytryptamine (5-HT) by guinea pig blood platelets. It was more potent than d-fenfluramine. Mazindol and d-fenfluramine decreased 5-hydroxy-indoleacetic acid formation in intact platelets but not in sonicated ones. The inhibitory effects of both drugs appeared to the competitive in nature and were markedly reduced in platelets suspended in plasma instead of in Tyrode solution. Mazindol neither decreased the stored endogenous 5-HT nor caused efflux of the labelled amine from preloaded platelets, whereas d-fenfluramine induced a significant release of the amine. It is concluded that mazindol, like d-fenfluramine, competes with 5-HT for the same transport mechanisms at the cytoplasmic membrane level but this effect is not accompanied, as is the case with d-fenfluramine, by a concomitant release of the amine.

Animals↗
PubMed1977

Effects of mazindol, fenfluramine and chlorimipramine on the 5-hydroxytryptamine uptake and storage mechanisms in rat brain: similarities and differences.

Mazindol and fenfluramine inhibited in vitro the uptake of 5-HT into rat forebrain synaptosomes, whether the synpatosomes were incubated in vitro with the drugs or obtained from animals pretreated in vitro. Chlorimipramine was also effective in this latter preparation. Dose-response relationships and time course of this effect for the various drugs were determined. Fenfluramine also caused release of 5-HT from preloaded synaptosomes in in vitro incubations. Mazindol did not. Brain 5-HT levels were measured after acute and chronic administration of mazindol, fenfluramine and chlorimipramine. Mazindol had no effect, fenfluramine was active in reducing brain 5-HT concentrations acutely and chlorimipramine only after chronic administration. Therefore, it seems that even a long lasting inhibition of the uptake, such as that induced by mazindol, is not sufficient, per se, to cause depletion of brain 5-HT.

Animals↗
PubMed1977

Mazindol and amphetamine as inhibitors of the uptake and releasers of 3H-dopamine by rat striatal synaptosomes.

The effects of mazindol, amphetamine and fenfluramine on uptake and release of 3H-DA by synaptosomes were studied in different systems. In in vitro incubations of 3H-DA with synaptosomes isolated from the caudate nucleus of the rat, mazindol inhibited the uptake of the radioactivity more potently than did amphetamine. When the synaptosomes were isolated from the caudate nuclei of rats treated in vivo with either mazindol or amphetamine, the uptake of 3H-DA during in vitro incuation was lower with synaptosomes of amphetamine-treated rats than with those of mazindol-treated rats. When synaptosomes of untreated rats were prelabelled with 3H-DA and incubated in the presence of amphetamine or of mazindol, amphetamine caused a greater release of radioactivity than did mazindol. Fenfluramine was without activity in all these systems. In spite of the quantitative differences, both amphetamine and mazindol appear to have similar effects on uptake and release of dopamine, and this may account for their analogous pharmacological profile.

Animals↗
PubMed1976

Behavioural effects of a new non-phenylethylamine anorexigenic agent: mazindol.

Mazindol, a new anorexigenic agent which possesses a different chemical structure from phenylethylamine derivatives such as amphetamine, causes anorexia along with increases in locomotor activity and body temperature. Mazindol also induces stereotyped behaviour and, if injected into rats with unilateral nigro-striatal lesions, causes turning towards the lesioned side. Mazindol-induced anorexia is antagonized by pretreatment with alpha-methyl-p-tyrosine or pimozide. Pimozide pretreatment prevents the rotation induced by Mazindol in rats with unilateral nigro-striatal lesions. The involvement of dopamine in the mechanism whereby Mazindol elicits anorexia and turning behaviour is discussed.

Animals↗
PubMed1976

Effects of mazindol, a non-phenylethylamine anorexigenic agent, on biogenic amine levels and turnover rate.

1 Mazindol is a new anorexigenic agent which possesses a different chemical structure from that of phenylethylamines, but shows a pharmacological profile similar to that of (+)-amphetamine. 2 Mazindol neither altered whole brain monoamine levels (noradrenaline (NA), dopamine, 5-hydroxytryptamine (5-HT)) nor changed NA levels in the hypothalamus or dopamine levels in the caudate nucleus. 3 Mazindol enhanced dopamine turnover rate in the caudate nucleus, as shown by the increased rate of dopamine decline after blockade of catecholamine synthesis by alpha-methyl-p-tyrosine and decreased the conversion index of (3H)-tyrosine into brain NA. 4 Mazindol administration did not modify pargyline-induced decline of 5-hydroxyindoleacetic acid suggesting that 5-HT turnover is not altered by this drug.

Animals↗
PubMed1976

Stimulatory role for brain serotoninergic system on prolactin secretion in the male rat.

Systemic administration of parachlorophenylalanine (PCPA, 100 mg/kg sc on alternate days X two times), a blocker of serotonin (5-HT) synthesis, considerably decreased brain 5-HT and plasma prolactin (PRL) levels in young male rats. Intraventricular (IVT) administration of 5,7-dihydroxytryptamine (5,7-DHT, 200 mug/20 mul), a neurotoxic drug which destroys 5-HT nerve terminals, induced, 3, 12, and 30 days after treatment, a marked depletion of brain 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) and considerably reduced plasma PRL levels at each time interval. Feeding of rat for up to 4 days with a tryptophan (TP)-deficient diet, caused a depletion of brain 5-HT and 5-HIAA contents and did not modify plasma PRL levels. Addition of TP (2 g/kg of diet) to the TP-deficient diet resulted in increased brain 5-HT and 5-HIAA contents and significantly increased PRL levels. These data provide evidence for the role of the 5-HT system in the maintenance of tonic PRL secretion.

5,6-Dihydroxytryptamine↗
PubMedDate not supplied

Catecholamine and serotonin depletion from rat spinal cord: effects on morphine and footshock induced analgesia.

Using a methodology that causes a selective degeneration of spinal cord catecholaminergic or serotoninergic pathways but not those of the brain, it has been possible to study more precisely the role played by the spinal cord monoaminergic systems that underly the mechanism through which morphine and endogenous opioids modulate nociceptive inputs. Both noradrenaline (NA) and serotonin (5-HT) appear to be involved: first, the noradrenergic and only subsequently, with higher doses of the opiate, the serotoninergic pathways.

5,7-Dihydroxytryptamine↗
PubMedDate not supplied

Differential relevance of beta-adrenoceptor subtypes in modulating the rat brown adipocytes function.

The potencies and intrinsic activities on cyclic AMP accumulation and lipolysis of various selective beta 3-adrenoceptor agonists were studied in brown adipocytes and compared to those of the nonselective, (-)-isoprenaline, and conventional beta 1- (dobutamine) and beta 2-adrenoceptor (salbutamol) agonists. (-)-Isoprenaline, dobutamine and salbutamol were more potent stimulants of lipolysis than of cyclic AMP accumulation, while the selective beta 3-adrenoceptor agonists had similar potencies for these two functions. Apparent pA2 values of the selective beta 1-(CGP20712A) and beta 2-adrenoceptor (ICI118551) antagonist for inhibition of adenylyl cyclase stimulation by (-)-isoprenaline and the beta 3-adrenoceptor agonists, BRL37344, SR58611A, and ICI215001, indicated that (-)-isoprenaline can stimulate the enzyme through a relevant beta 1-adrenergic component, while the other drugs activate the enzyme mainly by acting on the beta 3-adrenoceptors. On the contrary, antagonism of the lipolysis yielded apparent pA2 values for CGP20712A and ICI118551, suggesting that (-)-isoprenaline, like all the beta 3-adrenoceptor agonists, stimulated the brown adipose tissue lipid metabolism mainly through an action on beta 3-adrenoceptors.

Adipocytes↗