Mazindol Anorexia Is Mediated by Activation of Dopaminergic Mechanisms

Kruk, Zygmunt L.; Zarrindast, M.R.

doi:10.1111/j.1476-5381.1976.tb07713.x

Cited by 46 publications

(10 citation statements)

References 9 publications

(15 reference statements)

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“…showed a significant increase in locomotor activity. Pretreatment with reserpine plus AMPT, AOAA or pimozide inhibited the locomotor activity induced by ephedrine (Figure 4 (Kruk & Zarrindast, 1976).…”

Section: Drugsmentioning

confidence: 99%

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Dopamine‐like Properties of Ephedrine in Rat Brain

Zarrindast

1981

British J Pharmacology

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1 Ephedrine (3.1-50 mg/kg) was given intraperitoneally to rats and was found to cause a marked increase in spontaneous locomotor activity. 2 In rats with a unilateral lesion in the substantia nigra made by stereotaxic injection of 6-hydroxydopamine, ephedrine (12.5-150 mg/kg i.p.) caused a dose-dependent turning towards the lesioned side. 3 Turning behaviour and increase in locomotion produced by ephedrine were antagonized by pretreatment of the animals with pimozide, amino-oxyacetic acid or reserpine plus a-methyl-ptyrosine, but not by pretreatment with phenoxybenzamine, propranolol or methergoline. 4 In in vitro studies with synaptosomes prepared from rat brain, ephedrine blocked the uptake and caused the release of [3H]-dopamine. 5 Similar results with regard to locomotion and turning behaviour were obtained with (+)-amphetamine. 6 It is concluded that the increase in locomotion and turning behaviour produced by ephedrine is mediated through an indirect dopaminergic mechanism.

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Section: Drugsmentioning

confidence: 99%

“…Brains were removed immediately and striatal synaptosomes were prepared. The ability of ephedrine to inhibit uptake and to release [3H]-dopamine from synaptosomes was tested according to the method described previously (Kruk & Zarrindast, 1976). Statistical analysis was carried out by Student's t test.…”

Section: Turning Activitymentioning

confidence: 99%

Dopamine‐like Properties of Ephedrine in Rat Brain

Zarrindast

1981

British J Pharmacology

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Section: Dysfunction Of Monoamine Neurotransmission Seems To Contribumentioning

confidence: 99%

“…Mazindol binds with greater affinity to transporters for DA (K i ϭ 16 nM), 5-HT (K i ϭ 25 nM), and NE (K i ϭ 0.42 nM; Hyttel 1982) in rat brain synaptosomes, but has been characterized in vitro and in vivo as a potent inhibitor of DA and NE reuptake with less potency for 5-HT reuptake (Heikkila et al 1977; Sugrue et al 1977). The behavioral effects of mazindol have been attributed to catecholamine reuptake inhibition, especially that of DA, as DA receptor antagonists have been shown to attenuate both mazindol-induced anorexia and locomotor hyperactivity (Geveard and Takahashi 1999;Kruk and Zarrindast 1976).The present study was designed to assess the hyperactivity evoked by combinations of the SSRI fluvoxamine with mazindol and the involvement of 5-HT 2 receptors in the interactive behavioral effects of these two drugs. The 5-HT 2A and 5-HT 2C receptors were hypothesized to be particularly important because of the moderate to dense localization of both transcript and protein for these receptors in SN and VTA as well as DA terminal regions of rat forebrain (Abramowski et al 1995;Lopez-Gimenez et al 1997;Pompeiano et al 1994).…”

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Role of 5-HT2A and 5-HT2B/2C Receptors in the Behavioral Interactions Between Serotonin and Catecholamine Reuptake Inhibitors

McMahon

2001

Neuropsychopharmacology

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Dysfunction of monoamine neurotransmission seems to contribute to such pathopsychological states as depression, schizophrenia, and drug abuse. The present study examined the effects of the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) and antidepressant fluvoxamine on locomotor activity in rats following administration of the catecholamine reuptake inhibitor mazindol. Mazindol (1 mg/kg) did not alter locomotor activity; whereas, fluvoxamine (20 mg/kg) given alone induced a brief period of hypomotility. Hyperactivity was elicited in a doserelated manner when fluvoxamine (5-20 mg/kg) was combined with mazindol (1 mg/kg). The hyperactivity elicited by fluvoxamine (20 mg/kg) Several lines of evidence suggest that dopamine (DA) and serotonin (5-hydroxy tryptamine; 5-HT) interact in the central nervous system and that dysfunction of these neurotransmitters may contribute to such pathopsychological states as depression, schizophrenia, and drug abuse (Kahn and Davidson 1993;Kosten et al. 1998). The 5-HT-containing cell bodies of the dorsal raphe nucleus project to DA cell bodies of the ventral tegmental area (VTA) and substantia nigra (SN), and to their terminal fields in the prefrontal cortex (PFC), nucleus accumbens (NAc), and striatum (Hervé et al. 1987;Steinbush et al. 1981; Van der Kooy and Hattori 1980). The precise nature of the interaction between 5-HT and DA has been difficult to elucidate, with both inhibitory and excitatory roles for 5-HT identified with respect to the neural activity of DA neurons and the release of DA. For example, electrophysiological studies in vivo suggest an inhibitory influence of 5-HT on DA cell bodies of the VTA and SN (Prisco et al. 1994;Kelland et al. 1990), and 5-HT inhibits DA release from striatal slices (Ennis et al. 1981;Westfall and Tittermary 1982). On the other hand, in vivo microdialysis studies consistently demonstrate that local infusion of 5-HT increases DA efflux in the PFC, NAc, and striatum (Benloucif et al. NO . 3 1993; Gobert and Millan 1999; Iyer and Bradberry 1996;Parsons and Justice 1993), possibly through stimulation of one or more of the 14 5-HT receptor subtypes characterized to date (Barnes and Sharp 1999).The behavioral importance of 5-HT and DA interactions has been difficult to define. Much of this research has focused on modifications of behaviors evoked by enhanced DA neurotransmission consequent to psychostimulant administration. In early studies, reductions and enhancements of the locomotor stimulatory effects of cocaine (Scheel-Kruger et al. 1976) and amphetamine (Geyer et al. 1976) were reported following increased 5-HT synthesis or depletion of 5-HT, respectively. These and similar findings generated the hypothesis that 5-HT plays an inhibitory role in DA-mediated behavior. On the other hand, systemic administration of selective serotonin reuptake inhibitors (SSRIs) potentiated hyperactivity induced by amphetamine or cocaine in rats (Herges and Taylor 1998;Sills et al. 1999aSills et al. , 1999b, but not in mice (Arn...

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“…Mazindol, which is the first drug in therapy lacldng the phenylisopropyl backbone, seems to be a good tool for learning more about dopamine-mediated satiety. Mazindol seems to exert its anorectic effect by activating selectively a dopaminergic mechanism (Kruk and Zarrindast, 1976).…”

Section: Discussionmentioning

confidence: 99%

Satietin; a 50,000 dalton glycoprotein in human serum with potent, long-lasting and selective anorectic activity

Knoll

1984

J. Neural Transmission

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Satietin, a 50,000 dalton anorectic glycoprotein was isolated from human serum. Its isoelectric point is 7.0. It contains 14-15% amino acids and 70-75% carbohydrates. Its biological activity survives digestion with proteases and boiling. Satietin is a highly potent anorectic substance. The intracerebroventricular administration of 10-20 micrograms satietin suppresses food intake in rats during the first day of feeding after deprivation of food for 96 hours to half of the amount eaten by untreated controls (ID50). The onset of the effect can be detected within 30 minutes, the peak effect is reached within an hour. The effect lasts 24-30 hours. Satietin acts both at intravenous and subcutaneous administration (ID50 = 0.5-0.75 mg/kg) in rats deprived of food for 96 hours. The peak effect is reached within an hour and lasts over 24 hours. In contrast to the anorectic drugs in clinical use and to the endogenous anorectic substances (like cholecystokinin and calcitonin) satietin proved to be highly selective in suppressing food intake. Considering that satietin is widely distributed in the world of vertebrates, its concentration in the blood is amazingly high, its site of effect is in the central nervous system and it induces satiety without having any other detectable central or peripheral effect, the hypothesis was forwarded that satietin may play the role of a rate limiting blood-borne satiety signal in the negative feedback of food intake, i.e. serving as the essential chemical link connecting the gastrointestinal tract and the brain in the regulation of feeding.

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Mazindol Anorexia Is Mediated by Activation of Dopaminergic Mechanisms

Cited by 46 publications

References 9 publications

Dopamine‐like Properties of Ephedrine in Rat Brain

Dopamine‐like Properties of Ephedrine in Rat Brain

Role of 5-HT2A and 5-HT2B/2C Receptors in the Behavioral Interactions Between Serotonin and Catecholamine Reuptake Inhibitors

Satietin; a 50,000 dalton glycoprotein in human serum with potent, long-lasting and selective anorectic activity

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