Effect of disulfiram on turnover of 5-hydroxytryptamine in rat brain

Fukumori, Ryuji; Minegishi, Akemi; Satoh, Tetsuo; Kitagawa, Haruo; Yanaura, Saiζo

doi:10.1016/0024-3205(79)90383-7

Cited by 25 publications

(9 citation statements)

References 17 publications

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“…Disulfiram treatment increases serotonin’s precursor tryptophan, its metabolite 5-hydroxyindole acetic acid, and the hydroxylated product of tryptophan, 5-hydroxytryptophan (Fukumori et al , 1979, Fukumori et al , 1980, Nagendra et al , 1993, Nilsson & Tottmar, 1989). Since cocaine’s mechanism of action is through blockade of dopamine, norepinephrine, and serotonin transporters (Han & Gu, 2006), it is possible that disulfiram may be effective for the treatment of cocaine dependence, in part, through its action on serotonin.…”

Section: Introductionmentioning

confidence: 99%

Modifying the role of serotonergic 5‐HTTLPR and TPH2 variants on disulfiram treatment of cocaine addiction: a preliminary study

Nielsen

Harding

Hamon

et al. 2012

Genes Brain and Behavior

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Disulfiram is a cocaine pharmacotherapy that may act through increasing serotonin, benefiting patients with genetically low serotonin transporter levels (5-HTTLPR S′ allele carriers) and low serotonin synthesis (TPH2 A allele carriers). We stabilized 71 cocaine and opioid co-dependent patients on methadone for two weeks and randomized them into disulfiram and placebo groups for 10 weeks. We genotyped the SLC6A4 5-HTTLPR (rs4795541, rs25531) and TPH2 1125A>T (rs4290270) variants and evaluated their role in moderating disulfiram treatment for cocaine dependence. Cocaine positive urines dropped from 78% to 54% for the disulfiram group and from 77% to 76% for the placebo group among the 5-HTTLPR S′ allele carriers (F = 16.2; df = 1,301; P <0.0001). TPH2 A allele carriers responded better to disulfiram than placebo (F = 16.0; df = 1,223; P <0.0001). Patients with both an S′ allele and a TPH2 A allele reduced cocaine urines from 71% to 53% on disulfiram and had no change on placebo (F = 21.6; df = 1,185; P <0.00001).

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Section: Introductionmentioning

confidence: 99%

Modifying the role of serotonergic 5‐HTTLPR and TPH2 variants on disulfiram treatment of cocaine addiction: a preliminary study

Nielsen

Harding

Hamon

et al. 2012

Genes Brain and Behavior

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“…Fukumori et al (8) has reported that single treatment with DS (200 mg/kg, i.p.) does not inhibit soluble aldehyde dehydrogenase and monoamine ox idase activity, but significantly decreases mitochondrial aldehyde dehydrogenase activity in rat brain.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Anderson et al (7) have reported that gondotropin-induced pro lactin release is inhibited by pretreatment with DS in women with polycystic ovary syndrome and suggested that central dopaminergic tone was activated by the suppression of dopamine ,8-hydroxylase with DS. Furthermore, DS is reported to influence serotonin turnover in rat brain (8,9).…”

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confidence: 99%

Consecutive Treatment of Disulfiram Inhibits Ovarian Carbonyl Reductase Activity in Rats.

1992

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We investigated the effects of disulfiram (DS) on ovarian carbonyl re ductase activity in rats to determine the influence of DS on female reproductive func tion. Three consecutive treatments with DS significantly inhibited ovarian carbonyl re ductase activity as well as ovulation, dose-dependently. Single treatment with DS had no effect on ovarian carbonyl reductase activity. Our observations indicate that con secutive treatment with DS has an inhibitory action on female reproductive function, although DS is well-known to inhibit aldehyde dehydrogenase and dopamine ,8-hy droxylase.

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“…Fukumori et al (17) suggested that the increase of the neutral metabolite of 5-HT, 5-hydroxyindoleacetaldehyde (5 HIAAld), could modulate 5-HT turnover in the brain. Furthermore, Minegishi et al (30) suggested the product inhibition of MAO by 5-HIAAId from the result that when it was increased, 5-HT level in the brain was also increased in spite of no change in 5-HT synthesis rate.…”

Section: Discussionmentioning

confidence: 99%

“…Simultaneous determinations of 5-HT and 5-H IAA levels were carried out according to the fluorometric method of Peret-Cruet et al (16) with minor modi fication by Fukumori et al (17).…”

Section: Methodsmentioning

confidence: 99%

Suppression of pentylenetetrazol-induced seizures by hydralazine associated with 5-hydroxytryptaminergic system in rat brain.

1987

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Abstract-The effects of hydralazine on the central nervous system were studied in rats. Administration of hydralazine (10 mg/kg, i.p.) transiently, but significantly suppressed the seizures elicited by pentylenetetrazol (PTZ). The suppressive actions were potentiated in the animals pretreated with either reserpine or p chlorophenylalanine, but not a-methyltyrosine.Methysergide, an antagonist of 5-hydroxytryptamine (5-HT) receptors, could abolish the effect of hydralazine on the tonic component of the seizures, but unlikely that on the clonic one. Although 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels in the brain were both sig nificantly increased after the administration of hydralazine, the increased levels of 5-HIAA reached the peak level earlier than those of 5-HT did. In 5-HT turnover, hydralazine did not change the 5-HT synthesis rate, but the drug inhibited the elimination of 5-HIAA from the brain. The accumulation of 5-HIAA after the inhibition of the acid transport system by probenecid was transiently, but sig nificantly increased in the animals treated with hydralazine.The potency of the suppressive effects of hydralazine on PTZ-induced seizures was in parallel with the rate of 5-HIAA formation in the brain. These results suggest that hydralazine might antagonize the PTZ-induced seizures at least partly by modulating the activation in the central 5-HT-ergic system.

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Effect of disulfiram on turnover of 5-hydroxytryptamine in rat brain

Cited by 25 publications

References 17 publications

Modifying the role of serotonergic 5‐HTTLPR and TPH2 variants on disulfiram treatment of cocaine addiction: a preliminary study

Modifying the role of serotonergic 5‐HTTLPR and TPH2 variants on disulfiram treatment of cocaine addiction: a preliminary study

Consecutive Treatment of Disulfiram Inhibits Ovarian Carbonyl Reductase Activity in Rats.

Suppression of pentylenetetrazol-induced seizures by hydralazine associated with 5-hydroxytryptaminergic system in rat brain.

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