Role of monoamines in the anorexigenic actions of fenfluramine, amphetamine and p-chloromethamphetamine

Clineschmidt, Bradley V.; McGuffin, Jodie C.; Werner, Adam

doi:10.1016/0014-2999(74)90006-5

Cited by 76 publications

(10 citation statements)

References 19 publications

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“…Activation of 5-HT receptors by direct application of 5-HT (Kruk, 1973) or indirectly by release of 5-HT by drugs such as fenfluramine and norfenfluramine (Clineschmidt, McGuffin & Werner, 1974;Broekkamp, Weemaes & Van Rossum, 1975) can produce anorexia in rats. In the experiments reported here, methergoline, a specific 5-HT receptor blocker (Beretta, Ferrini & Glasser, 1965), did not antagonize the anorectic response to mazindol; thus it was concluded that activation of 5-HT mechanisms is not involved in mediating mazindol anorexia.…”

Section: Discussionmentioning

confidence: 99%

Mazindol Anorexia Is Mediated by Activation of Dopaminergic Mechanisms

Kruk

Zarrindast

1976

British J Pharmacology

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1 Anorexia in rats following injections of mazindol (0.1-8 mg/kg i.p.) could be antagonized by pretreatment with a dopamine receptor blocker (pimozide) but not by pretreatment with an aadrenoceptor blocker (phenoxybenzamine), a P-adrenoceptor blocker ((-)-propranolol), or a 5-hydroxytryptamine receptor blocker (methergoline). 2 In rats with a unilateral lesion in the substantia nigra made by stereotaxic injection of 6-hydroxydopamine, mazindol caused a dose-dependent turning towards the lesioned side, indicating an indirect mechanism of action. This effect could be antagonized by pretreatment with a dopamine receptor blocker.3 In rats pretreated with reserpine and a-methyl-p-tyrosine, mazindol did not have any motor stimulant action. 4 In vitro studies with synaptosomes prepared from rat brain, indicated that mazindol blocks uptake and causes release of dopamine. S It is concluded that the anorectic action of mazindol is mediated by a dopaminergic mechanism.

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Section: Discussionmentioning

confidence: 99%

Mazindol Anorexia Is Mediated by Activation of Dopaminergic Mechanisms

Kruk

Zarrindast

1976

British J Pharmacology

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“…In contrast to the original amphetamines, fenfluramine had no addictive properties allowing its usage as an appetite suppressant on a wider scale. Brain lesions and pharmacological experiments using 5-HT antagonists [22][23][24][25][26] revealed that the hypophagic effect of fenfluramine is indeed based on its serotonergic properties. The brain serotonergic system originates from raphe nuclei in the brainstem [14].…”

Section: Brain 5-ht and Satietymentioning

confidence: 99%

Serotonin controlling feeding and satiety

Voigt

Fink

2015

Behavioural Brain Research

257

167

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Serotonin has been implicated in the control of satiety for almost four decades. Historically, the insight that the appetite suppressant effect of fenfluramine is linked to serotonin has stimulated interest in and research into the role of this neurotransmitter in satiety. Various rodent models, including transgenic models, have been developed to identify the involved 5-HT receptor subtypes. This approach also required the availability of receptor ligands of different selectivity, and behavioural techniques had to be developed simultaneously which allow differentiating between unspecific pharmacological effects of these ligands and 'true' 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 3 IntroductionWhat are the behavioural and physiological mechanisms that promote satiety? How is satiety defined? Satiety can be seen as a behavioural state which arises from food consumption and suppresses the initiation of eating for a particular period of time [1]. This description alone suggests a high degree of complexity as peripheral post-ingestive and post-absorptive signals need to be relayed to the brain where they are integrated with other signals to produce (or not) the behavioural state called satiety. The state of satiety is brought about a process called satiation, where sensory, cognitive and early post-ingestive mechanisms bring feeding to a halt and thus stopping a meal. Promoting satiation alone must not necessarily lead to reduced total food intake as the frequency of meals could be increased subsequently. Many peripheral and brain mechanisms have been identified that are involved in the expression satiety and it has been suggested that serotonin accelerates satiation and prolongs satiety [2]. In the following, we will review the role of serotonin in satiety in more detail 1 . The reader will see that, despite immense progress made during the last years, the field is still far from being resolved.As serotonin (5-Hydroxytryptamine; 5-HT) is a phylogenetically old neurotransmitter, various functions had time to evolve in different phyla, but maybe also in different species. 5-HT receptors exist in animal cells for millions of years and they are as old as adrenoreceptors ore some peptide receptors, possibly even older [5,6]. Even in invertebrates such as molluscs (Aplysia californica) and annelids (Hirudo medicinalis), 5-HT might functionally be related to food intake [7]. 5-HT is involved in feeding even in the honeybee where it has separate effects in the gut and in the insect brain [8]. In general, however, 5-HT seems rather to be involved in appetitive behaviours in invertebrates whereas it has more of a satiating effect in vertebrates [9]. In general, 5-HT neurons seem to be more extensively distributed throughout the body in lower animals than in higher animals including mammals where 5-HT neurones...

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“…Several early studies sought evidence for serotonergic-mediation of fenfluramine's anorectic effect using serotonin (5-HT) receptor antagonists. For example, fenfluramine's effect on food intake has been blocked by non-selective 5-HT receptor antagonists, methysergide, metergoline, cyproheptadine and cinanserin (Jespersen and Scheel-Krfiger 1973 ;Clineschmidt et al 1974;Barrett and McSharry 1975;Blundell and Latham 1980). In addition, more recent studies using d-fenfluramine, which interacts more selectively with 5-HT mechanisms than/-fenfluramine (Garattini et al 1986a;Invernizzi et al 1986), have shown that its effect on food intake could be blocked by the centrally-active antagonist metergoline, but not by the peripheral 5-HT receptor antagonist xylamidine (Borsini et al 1982(Borsini et al , 1985.…”

mentioning

confidence: 98%

Evidence that d-fenfluramine anorexia is mediated by 5-HT1 receptors

1989

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The effects of eight serotonin (5-HT) receptor antagonists on the anorectic effect of d-fenfluramine (3.0 mg/kg, IP) were examined in a test of sweet mash consumption, using non-deprived male rats. d-Fenfluramine's effect was attenuated by the mixed 5-HT1/5-HT2 receptor antagonists, methiothepin and metergoline; by the 5-HT2 receptor antagonist ritanserin; and by (+/-)cyanopindolol, a mixed 5-HT1A/5-HT1B receptor antagonist. In contrast, d-fenfluramine's effect was not antagonised by the 5-HT2 receptor antagonists ketanserin and ICI 169 369; the 5-HT3 receptor antagonist ICS 205 930; or by xylamidine, a peripheral 5-HT receptor antagonist. In this feeding model, none of the 5-HT antagonists, when tested alone, had any effect to increase palatable food consumption. The pattern of results obtained strongly suggest that central 5-HT1 receptors play an important role in the mediation of d-fenfluramine-induced anorexia.

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Role of monoamines in the anorexigenic actions of fenfluramine, amphetamine and p-chloromethamphetamine

Cited by 76 publications

References 19 publications

Mazindol Anorexia Is Mediated by Activation of Dopaminergic Mechanisms

Mazindol Anorexia Is Mediated by Activation of Dopaminergic Mechanisms

Serotonin controlling feeding and satiety

Evidence that d-fenfluramine anorexia is mediated by 5-HT1 receptors

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