Antagonism of central effects of tryptamine and 5-hydroxytryptophan by 1,6-dimethyl-8?-carbobenzyloxy-aminomethyl-10?-ergoline

Ferrini, R; Glässer, A.

doi:10.1007/bf00407859

Cited by 58 publications

(9 citation statements)

References 5 publications

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“…We have used both automated activity recordings and ratings of components of the behaviour and have examined the effects of the three putative 5-HT antagonists, methysergide, methergoline and propranolol. Various behavioural and pharmacological findings suggest that both methysergide (Banna & Anderson, 1973) and methergoline (Ferrini & Glasser, 1965;Fuxe, Agnati & Everitt, 1975) are 5-HT receptor antagonists. More recently the ,B-adrenoceptor antagonist (-)-propranolol has been shown to inhibit the tranylcypromine/L-tryptophan hyperactivity (Green & Grahame-Smith, 1976b) and Middlemiss, Blakeborough & Leather (1977) reported that (-)-propranolol was as potent as methysergide in inhibiting 5-HT binding in brain.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Putative 5‐hydroxytryptamine Antagonists on the Behaviour Produced by Administration of Tranylcypromine and L‐tryptophan or Tranylcypromine and L‐dopa to Rats

Deakin

Green

1978

British J Pharmacology

147

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1 The putative 5-hydroxytryptamine (5-HT) receptor blocking drugs methysergide (10 mg/kg) and methergoline (5 mg/kg) were found to abolish some components of the hyperactivity syndrome, including head weaving and forepaw treading, which follow administration to rats of tranylcypromine (20 mg/kg) and L-tryptophan (100 mg/kg). Hyperactivity and hyper-reactivity were potentiated with a resultant increase in automated locomotor activity counts. In contrast (-)-propranolol (20 mg/kg) inhibited all features of the syndrome. The same results were obtained with these drugs when the behaviour was elicited by p-chloroamphetamine (10 mg/kg) or by tranylcypromine and tryptamine (10 mg/kg).2 Methysergide and methergoline had similar effects on the syndrome produced by tranylcypromine and L-DOPA (50 mg/kg) whereas propranolol was without effect. 3 None of the putative 5-HT receptor antagonists affected brain 5-HT turnover as assessed by rate of accumulation of 5-HT following monoamine oxidase inhibition with tranylcypromine. 4 Microinjections of 5,7-dihydroxytryptamine into the spinal cord resulted in a 70% fall in cord 5-HT concentrations without an effect on brain 5-HT concentrations. The behavioural response to the putative 5-HT receptor agonist, 5-methoxy N,N-dimethyltryptamine (2 mg/kg), was potentiated in these animals suggesting that 5-HT receptors become supersensitive on denervation, and that some components of the behavioural syndrome are mediated by spinal cord 5-HT receptors. 5 Pretreatment with a-methyl p-tyrosine (2 x 200 mg/kg) delayed the onset of all components of the behaviour elicited by tranylcypromine/L-tryptophan by 60 min, indicating an involvement of catecholamines in the syndrome. 6 p-Chloroamphetamine-induced 5-HT depletion had no effect on any component of the tranylcypromine-L-DOPA behaviour.

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Section: Introductionmentioning

confidence: 99%

The Effects of Putative 5‐hydroxytryptamine Antagonists on the Behaviour Produced by Administration of Tranylcypromine and L‐tryptophan or Tranylcypromine and L‐dopa to Rats

Deakin

Green

1978

British J Pharmacology

147

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“…(CNS) are the head twitch response provoked by administration of 5-hydroxytryptophan (5-HTP) and the clonus of the forepaws induced by injection of tryptamine. Even for well-known indoleamine antagonists such as cyproheptadine (Stone, Wenger, Ludden, Stavorski & Ross, 1961), cinanserin (Rubin, Piala, Burke & Craver, 1964), methergoline (Ferrini & Glasser, 1965) and methysergide (Doepfner & Cerletti, 1958) 5-hydroxytryptophan-elicited head twitch The head-twitch response was assessed on a quantal basis as previously described in mice by Corne, Pickering & Warner (1963). The antagonists were administered 30 min prior to 5-HTP (270 mg/kg) and the number of animals exhibiting at least one head twitch was determined 1 h later.…”

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confidence: 99%

Indoleamine Antagonists: Relative Potencies as Inhibitors of Tryptamine‐ and 5‐hydroxytryptophan‐evoked Responses

Clineschmidt¹,

Lotti²

1974

British J Pharmacology

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“…Reduction of the anorectic effect of MK-212 by antagonists of 5-hydroxytryptamine Pretreatment with methergoline (Beretta, Glasser, Nobili & Silvestri, 1965;Ferrini & Glasser, 1965;Clineschmidt & Lotti, 1974) significantly reduced the magnitude of the anorectic response to MK-212, 1.5 (approximate ED50) and 3 mg/kg (Figure 1). Methergoline alone did not affect food consumption.…”

Section: Resultsmentioning

confidence: 97%

“…However, such an interpretation requires that methergoline can also inhibit some undefined non-5-HT-mimetic mechanism operative at the low dose of MK-212. The selectivity of methergoline as an indoleamine antagonist (Ferrini & Glasser, 1965;Beretta et al, 1965;Fuxe, Agnati & Everitt, 1975a;Sastry & Phillis, 1976) mitigates this possibility. In any event, the fact that three structurally dissimilar anti-5-HT agents significantly reduced the anorectic response to a high dose of MK-212 clearly points to an underlying 5-HT-like mode of action.…”

Section: Discussionmentioning

confidence: 99%

A 5‐hydroxytryptamine‐like Mode of Anorectic Action for 6‐chloro‐2‐[1‐piperazinyl]‐pyrazine (Mk‐212)

Clineschmidt¹,

McGuffin²,

Pflueger³

et al. 1978

British J Pharmacology

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1 The mechanism of the reduction in food consumption elicited by 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212) administered systemically was investigated in the rat. (±)-Fenfluramine and (+)-amphetamine were included in some studies for comparative purposes. 2 Pretreatment with methergoline, a 5-hydroxytryptamine (5-HT) antagonist, reduced the magnitude of the anorectic effect of 1.5 and 3 mg/kg of MK-212, while the anti-5-HT agents, cyproheptadine and cinanserin, were likewise effective against the 3 mg/kg dose. 3 Xylamidine, an antagonist of 5-HT that penetrates poorly into the central nervous system, completely blocked the decrease in food intake caused by 5-HT administered peripherally, while not antagonizing an equianorectic dose of MK-212. 4 Reduction of brain 5-HT by intraventricular injection of 5,6-dihydroxytryptamine, intraperitoneal administration of p-chloroamphetamine or placement of a lesion in the region of the median raphe nucleus diminished the anorectic response to 3 mg/kg of MK-212. The anorectic effect of amphetamine was reduced by p-chloroamphetamine or lesion in the raphe, but not by 5,6-dihydroxytryptamine. The decrease in food consumption produced by 1.5 mg/kg of MK-212 was antagonized by prior treatment with p-chloroamphetamine, but not by 5,6-dihydroxytryptamine. 5 Haloperidol, which blocks receptors for dopamine, antagonized the anorexigenic effect of amphetamine, but was ineffective in offsetting the action of MK-212, 3 mg/kg. 6 Pretreatment with chlorimipramine to inhibit the 5-hydroxytryptaminergic uptake mechanism did not affect the anorectic response to 3 mg/kg of MK-212, whereas the response to fenfluramine was diminished. 7 The results indicate that the anorectic action of MK-212 involves a 5-HT-like component which is more evident at the higher dose level of the compound. The anorexigenic property of MK-212 may depend, at least partly, upon the integrity of 5-HT-containing neurones in the central nervous system.

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Antagonism of central effects of tryptamine and 5-hydroxytryptophan by 1,6-dimethyl-8?-carbobenzyloxy-aminomethyl-10?-ergoline

Cited by 58 publications

References 5 publications

The Effects of Putative 5‐hydroxytryptamine Antagonists on the Behaviour Produced by Administration of Tranylcypromine and L‐tryptophan or Tranylcypromine and L‐dopa to Rats

The Effects of Putative 5‐hydroxytryptamine Antagonists on the Behaviour Produced by Administration of Tranylcypromine and L‐tryptophan or Tranylcypromine and L‐dopa to Rats

Indoleamine Antagonists: Relative Potencies as Inhibitors of Tryptamine‐ and 5‐hydroxytryptophan‐evoked Responses

A 5‐hydroxytryptamine‐like Mode of Anorectic Action for 6‐chloro‐2‐[1‐piperazinyl]‐pyrazine (Mk‐212)

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