Effect of Ethanol on Neurohumoral Amine Metabolism

Feldstein, Aaron

doi:10.1007/978-1-4615-6525-3_4

Cited by 36 publications

(12 citation statements)

References 121 publications

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“…55,56 As a consequence, the molar ratio of the oxidative products (e.g., 5-HIAA) to that of the reductive products (e.g., 5-HTOL) in the urine decreases after consuming ethanol. While the effects of such metabolic shift on the biochemistry, physiology, and ethanol drinking behavior of humans and laboratory animals are still unknown, it was suggested that an increase in the steady-state concentration of the biogenic aldehydes could account for such alterations in monoamine metabolism.…”

Section: Daidzin May Suppress Ethanol Consumption By Mimicking the Efmentioning

confidence: 99%

Anti‐dipsotropic isoflavones: The potential therapeutic agents for alcohol dependence

Keung

2003

Medicinal Research Reviews

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Daidzin is the active principle of Radix puerariae (RP), an herbal remedy that has been used apparently safely and effectively for the treatment of "alcohol addiction" in China for more than a millennium. It has been shown to reduce alcohol consumption in all animal models tested to date. A link between daidzin's capacity to reduce alcohol consumption and its ability to increase liver mitochondrial monoamine oxidase (MAO): aldehyde dehydrogenase (ALDH-2) activity ratio has been established. Daidzin analogs that potently inhibit ALDH-2 but not MAO are the most anti-dipsotropic, whereas those that also inhibit MAO are not. On the basis of these findings, it was proposed that the liver mitochondrial MAO-ALDH-2 pathway is the primary site of action of daidzin and that a biogenic aldehyde derived from the action of MAO mediates its anti-dipsotropic action. Therefore, to design and synthesize more potent anti-dipsotropic analogs, structural features that would enhance ALDH-2 inhibition and/or decrease MAO inhibition needed to be evaluated. Structure-activity-relationship (SAR) studies have revealed that a sufficient set of criteria for a potent anti-dipsotropic analog is an isoflavone with a free 4'-OH function and a straight-chain alkyl at the 7 position that has a terminal polar function such as -OH, -COOH, or -NH2. The preferable chain lengths for the 7-O-omega-carboxy, 7-O-omega-hydroxy, and 7-O-omega-amino substituents are 5 < or = n < or = 10, 2 < or = n < or = 6, and n > or = 4, respectively. Analogs that meet these criteria have increased potency for ALDH-2 inhibition and/or decreased potency for MAO inhibition and are, therefore, likely to be potent anti-dipsotropic agents.

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Section: Daidzin May Suppress Ethanol Consumption By Mimicking the Efmentioning

confidence: 99%

Anti‐dipsotropic isoflavones: The potential therapeutic agents for alcohol dependence

Keung

2003

Medicinal Research Reviews

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“…The involvement of biogenic amines in the mediation of central and peripheral effects of ethanol has been postulated by several authors (for a review see Feldstein, 1971;Truitt & Walsh, 1971;Lahti, 1975).…”

Section: Introductionmentioning

confidence: 99%

Brain Concentrations of Biogenic Amine Metabolites in Acutely Treated and Ethanol‐dependent Rats

Karoum

Wyatt

Majchrowicz

1976

British J Pharmacology

132

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Mass fragmentography was used to measure whole brain concentrations of some of the major metabolites of tyramine, octopamine, dopamine and noradrenaline in acutely treated and in ethanoldependent rats. Treatments with ethanol, either acutely or chronically, failed to alter significantly brain concentration of p‐hydroxyphenylacetic and p‐hydroxymandelic acid (metabolites derived from tyramine and octopamine respectively). The effect on catecholamine metabolites was marked and therefore suggests that ethanol is selective in its effect on central metabolism of biogenic amines. Acute ethanol treatment significantly increased brain concentration of homovanillic acid (HVA), 3,4‐dihydroxyphenylacetic acid (DOPAC) and 3‐methoxy‐4‐hydroxyphenylglycol (MHPG). Vanilmandelic acid (VMA) was not affected. All four metabolites (HVA, DOPAC, MHPG and VMA) were increased in the brains of rats rendered dependent on ethanol while still intoxicated (blood ethanol levels above 200 mg/dl). In ethanol‐dependent rats undergoing ethanol withdrawal syndrome (no ethanol present in blood), the brain concentrations of HVA and DOPAC were normal while those of MHPG and VMA continued to be elevated. From the decline in the concentrations of HVA and DOPAC after 50 mg pargyline/kg in control rats and rats acutely treated with ethanol, it was concluded that ethanol has no effect on the transport of phenolic acids across the blood brain barrier. No reversal in the metabolism of catecholamines from an oxidative to a reductive pathway, analogous to that produced by ethanol in the periphery, could be established in the brain. The increase in catecholamine metabolite concentrations after ethanol treatment, either acute or chronic, were interpreted as manifestations of increases catecholamine turnover.

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“…Many researchers have presented evidence that EtOH produces a decrease in NE release in the animal brain (Carlsson et al 1973;Thadani et al 1977). EtOH appears to have several effects on NE release, including: (a) inhibition of neuronal membrane uptake of circulating NE, (b) inhibition of neuronal membrane reuptake of NE discharged into the synaptic cleft on nerve stimulation, and (c) inhibition of uptake of NE into storage granules (Feldstein 1971). Acetaldehyde (AcH), a proximal metabolite of EtOH, is a highly toxic compound, and has been reported to mediate psychic effects such as feelings of well-being and euphoria, caused by EtOH drinking.…”

Section: Introductionmentioning

confidence: 98%

“…Acetaldehyde (AcH), a proximal metabolite of EtOH, is a highly toxic compound, and has been reported to mediate psychic effects such as feelings of well-being and euphoria, caused by EtOH drinking. AcH in high concentrations may produce CNS depression, abnormal gait, ataxia, loss of equilibrium and motion in animals (Feldstein 1971). These AcH-induced effects are more commonly seen in Asians and some American Indians due to the deficiency in aldehyde dehydrogenase 2 (ALDH2) in these groups (Mizoi et al 1983;Wolff 1972Wolff , 1973.…”

Section: Introductionmentioning

confidence: 99%

Failure of ethanol and acetaldehyde to alter in vivo norepinephrine release in the striatum and hippocampus of rats

et al. 2004

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The effect of ethanol (EtOH) and acetaldehyde (AcH) on norepinephrine (NE) release was examined in the striatum and hippocampus of freely moving rats by means of in vivo microdialysis coupled with high-performance liquid chromatography and an electrochemical detector. Rats were treated intraperitoneally with EtOH (1 g/kg) or cyanamide (CY, 50 mg/kg, a potent aldehyde dehydrogenase inhibitor) plus EtOH (1 g/kg). No significant difference in NE levels in the dialysates was observed in the striatum and hippocampus in either the EtOH or CY+EtOH groups. NE levels in the hippocampal dialysates were about fivefolds higher than those in the striatum. The concentration of EtOH and AcH in the striatal dialysate reached a peak at 30 min after EtOH dosing and then gradually decreased in the CY+EtOH group. In the EtOH group the striatal concentration of EtOH also reached a peak at 30 min after EtOH dosing, and then gradually decreased while AcH was not detected. The present study suggests that there is no in vivo effect of brain EtOH or AcH on NE release in the striatum and hippocampus of awake rats.

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Effect of Ethanol on Neurohumoral Amine Metabolism

Cited by 36 publications

References 121 publications

Anti‐dipsotropic isoflavones: The potential therapeutic agents for alcohol dependence

Anti‐dipsotropic isoflavones: The potential therapeutic agents for alcohol dependence

Brain Concentrations of Biogenic Amine Metabolites in Acutely Treated and Ethanol‐dependent Rats

Failure of ethanol and acetaldehyde to alter in vivo norepinephrine release in the striatum and hippocampus of rats

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