Effects of antihistamines on fenfluramine-induced depletion of indoles in the brain of rats

Yeh, S.Y.

doi:10.1002/(sici)1098-2396(19990615)32:4<301::aid-syn6>3.0.co;2-g

Cited by 6 publications

(6 citation statements)

References 41 publications

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“…The substituted amphetamines-[e.g. p-chloromethamphetamine (PCMA)-, p-chloroamphetamine (PCA)-, 4-methyl-␣-ethyl-m-tyramine (MET)-and fenfluramine (FEN)]-induced depletion of 5-HT is attenuated by CPA (Meek et al, 1971;Schmidt 1987;Fuller, et al, 1975;Carlsson and Lindqvist, 1969;Yeh, 1999b). The mechanism(s) of these substituted amphetamine-induced depletion of 5-HT is not clear but may share some mechanism(s) of MDMA-induced depletion of 5-HT.…”

Section: Discussionmentioning

confidence: 99%

“…Saline was used as the control, both alone or co-injection with MDMA or the antihistamines. The doses of CPA (10, 20, and 25 mg/kg) for the present study were chosen from the literature (Carlsson and Lindqvist, 1969), the results of interactions of MDMA and CPA (see below), and after determining that a 5 mg/kg dose of CPA did not attenuate fenfluramine-induced depletion of 5-HT (Yeh, 1999b). The doses of DIPH, TRIP, and PYRI are based on that of CPA.…”

Section: Dose Regimenmentioning

confidence: 99%

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Effects of antihistamines on 3,4-methylenedioxymethamphetamine-induced depletion of serotonin in rats

Yeh

Dersch

Rothman

et al. 1999

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This study investigated the effects of chlorpheniramine (CPA, 10-25 mg/kg), diphenhydramine (DIPH, 20 mg/kg), tripelennamine (TRIP, 20 mg/kg), and pyrilamine (PYRI, 20 mg/kg) on 3, 4-methylenedioxymethamphetamine (MDMA, 20 mg/kg x 2)-induced hyperthermia and depletion of indoles in rat brains, on the uptake of serotonin and dopamine into rat synaptosomes, on the binding affinity of CPA for biogenic amine transporters in the synaptosomes of rat brain, and on the scavenging hydroxyl free radicals activity. Rats were treated with two injections of MDMA, CPA, DIPH, TRIP, PYRI, and saline, alone or in combination of MDMA with one of the antihistamines, 6 h apart and sacrificed 5 days later. Rectal temperature was measured prior to and hourly following the drug injections for 13 h. As compared to saline controls, MDMA increased body temperature and decreased levels of indoles, measured by HPLC, in several brain regions of rats. CPA attenuated and DIPH had no effect on MDMA-induced hyperthermia, yet both attenuated the depletion of indoles, whereas PYRI and TRIP potentiated these effects. CPA inhibited the binding of [(3)H]paroxetine and [(3)H]nisoxetine to the synaptosomes of cerebral cortex and of [(3)H]win 35,428 to the synaptosomes of striatum. CPA, DIPH, TRIP, and PYRI inhibited [(3)H]serotonin uptake. CPA, PYRI, and TRIP, but not DIPH, scavenge hydroxyl radicals. Possible mechanisms of the different effects of the antihistamines on MDMA-induced hyperthermia and depletion of serotonin are discussed. Published 1999 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Section: Dose Regimenmentioning

confidence: 99%

Effects of antihistamines on 3,4-methylenedioxymethamphetamine-induced depletion of serotonin in rats

Yeh

Dersch

Rothman

et al. 1999

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“…In addition, the relationship between hyperthermia and the neurotoxic effects of the substituted amphetamines has been explored. Fenfluramine toxicity is exacerbated when administered in ambient temperatures greater than 28ae (Malberg & Seiden 1997;Stewart et al 1997), however, is not blocked by substances which intensify fenfluramine-induced hypothermia (Farfel & Seiden 1995;Yeh 1999). While studies have established a relationship between methamphetamine-induced hyperthermia and serotonergic neurotoxicity (Boyer et al 1992;Farfel et al 1992;Farfel & Seiden, 1995), the two effects are dissociable (Farfel & Seiden 1995;Ali & Itzhak 1998;Haughey et al 2000) and therefore, most likely independent of each other.…”

Section: Discussionmentioning

confidence: 99%

“…Fenfluramine also produces fragmentation of DNA, a marker of apoptosis, in serotonergic cells (Bengel et al 1998) as well as neuronal degeneration evidenced by a localized flourescent marker (Schmued et al 1999). These changes are all accompanied by a long-term depletion of brain serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) (Steranka & Sanders-Bush 1979;Kleven & Seiden 1989;Zaczek et al 1990;Malberg & Seiden 1997;Stewart et al 1997;Halladay et al 1998;Yeh 1999). Furthermore, the magnitude of this neurochemical depletion paralled that of the loss of serotonin uptake sites (Zaczek et al 1990).…”

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confidence: 99%

Role of Monoamine Oxidase Inhibition and Monoamine Depletion in Fenfluramine‐Induced Neurotoxicity and Serotonin Release

Halladay¹,

Kirschner²,

Hesse³

et al. 2001

Pharmacology & Toxicology

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The role of both monoamine synthesis and monoamine oxidase inhibition in mediating the fenfluramine-induced damage to serotonin neurones was examined; as pretreatment agents, both alpha-methyl-para-tyrosine (AMPT) and parachlorophenylalanine (PCPA) were used to deplete dopamine and serotonin, respectively, while clorgyline and deprenyl were used to inhibit monoamine oxidase types A and B. While both AMPT and deprenyl did not alter fenfluramineinduced serotonin or 5-hydroxyindoleacetic acid (5-HIAA) depletion in any area, PCPA did partially reduce the serotonin depletion in the hippocampus and hypothalamus. Although pretreatment with clorgyline did not significantly alter fenfluramine-induced serotonin depletion, it did produce a 65% mortality rate in animals treated with both drugs. Both PCPA and clorgyline significantly increased the depletion of striatal 5-HIAA concentration consequent to fenfluramine; however, these drugs also produced a long-term depletion of striatal 5-HIAA when administered alone, therefore, the changes seen after the coadministration with fenfluramine may be viewed as additive. Finally, acute PCPA pretreatment attenuated the rapid rise in 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (homovanillic acid) induced by fenfluramine, and acute clorgyline reversed the drop in serotonin and rise in 5-HIAA induced by fenfluramine. These results indicate that the rapid increase in dopamine activity induced by fenfluramine is partially dependent on serotonin concentration and release and that the mechanism of fenfluramine-induced toxicity is unlike that of the other substituted amphetamines.

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“…The role of histamine was evaluated by using a number of different antihistamines with different speci®city and receptor af®nity, e.g. amitriptyline 12,13 , cyproheptadine 12±15 , pyrilamine 16 and meclizine 15 .…”

Section: Introductionmentioning

confidence: 99%

Role of mast cells in the development of pancreatitis-induced multiple organ dysfunction

Dib

Zhao

Wang

et al. 2002

British Journal of Surgery

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Background: Activated mast cells can produce and release a number of in¯ammatory mediators involved in the pathophysiology of acute conditions. The aim of the present study was to evaluate the role of activated tissue mast cells in the pathogenesis of multiple organ dysfunction syndrome following acute pancreatitis (AP). Methods: AP was induced by the intraductal infusion of 5 per cent sodium taurodeoxycholate in the rat. Some 30 min before induction of AP, a mast cell stabilizer (sodium cromoglycate (SCG)) or antihistamines (pyrilamine, cyproheptadine, meclizine and amitriptyline) were administered intraperitoneally. Plasma exudation of radiolabelled albumin, histamine, myeloperoxidase (MPO), monocyte chemoattractant protein (MCP) 1 and adhesion molecules (platelet endothelial cell adhesion molecule (PECAM) 1 and L-selectin) were measured.Results: The mast cell stabilizer signi®cantly reduced plasma exudation in the pancreas, colon and lungs (P < 0´05), decreased the release of histamine at 1 h (P < 0´05), and reduced MPO activity and MCP-1 levels in the colon and lungs (P < 0´05) but not in the pancreas. Expression of PECAM-1 and L-selectin on total circulating leucocytes in rats with AP and SCG pretreatment did not differ from that in sham controls, while levels in animals that had AP and saline pretreatment were half of those seen following sham operation.Conclusion: Activation of mast cells after induction of AP is involved in the development of endothelial barrier dysfunction in both the pancreas and extrapancreatic organs/tissues, particularly in the lungs and colon. This may, at least partly, contribute to the sequential development of multiple organ dysfunction and organ/tissue-speci®c endothelial barrier dysfunction.

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Effects of antihistamines on fenfluramine-induced depletion of indoles in the brain of rats

Cited by 6 publications

References 41 publications

Effects of antihistamines on 3,4-methylenedioxymethamphetamine-induced depletion of serotonin in rats

Effects of antihistamines on 3,4-methylenedioxymethamphetamine-induced depletion of serotonin in rats

Role of Monoamine Oxidase Inhibition and Monoamine Depletion in Fenfluramine‐Induced Neurotoxicity and Serotonin Release

Role of mast cells in the development of pancreatitis-induced multiple organ dysfunction

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