Effects of 3-&lt;i&gt;O&lt;/i&gt;-Methyldopa, &lt;small&gt;L&lt;/small&gt;-3,4-Dihydroxyphenylalanine Metabolite, on Locomotor Activity and Dopamine Turnover in Rats

Onzawa, Yoritaka; Kimura, Yasuhiro; Uzuhashi, Kengo; Shirasuna, Megumi; Hirosawa, Tasuku; Taogoshi, Takanori; Kihira, Kenji

doi:10.1248/bpb.b110714

Cited by 11 publications

(11 citation statements)

References 22 publications

(24 reference statements)

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“…The current results indicated that striatal AADC levels in the treatment groups increased within 48 h compared with the control group, which was consistent with the observation that striatal DA levels within 48 h were elevated compared with levels in the hippocampus and cortex. Furthermore, DA may be degraded into DOPAC by MAO-B and into HVA by COMT (5,6). In the present study, striatal levels of MAO-B and COMT in the treatment groups were reduced compared with the control group, which may explain why the (DOPAC + HVA)/DA ratio in the striatum was reduced compared with the control group during 48 h.…”

Section: Discussionsupporting

confidence: 45%

“…L-dopa is subsequently converted into DA by aromatic amino acid decarboxylase (AADC) (4). In addition, DA is converted into 3,4-dihydroxyphenylacetic acid (DOPAC) by monoamine oxidase B (MAO-B) (5), and into homovanillic acid (HVA) by catechol-O-methyltransferase (COMT) (6). Therefore, L-dopa, DA, DOPAC, HVA, AADC, MAO-B, COMT and TH may be implicated in the pathogenesis of PD.…”

Section: Introductionmentioning

confidence: 99%

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Dynamic changes of five neurotransmitters and their related enzymes in various rat tissues following β-asarone and levodopa co-administration

Huang

Deng

Fang

et al. 2015

Experimental and Therapeutic Medicine

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The aim of the present study was to investigate the dynamic changes of five neurotransmitters and their associated enzymes in the rat plasma and brain tissues following the co-administration of β-asarone and levodopa (L-dopa). The rats were divided into five groups, including the control group and four treatment groups that were intragastrically co-administered β-asarone and L-dopa and sacrificed at 1, 5, 18 and 48 h, respectively. Neurotransmitter levels in the brain tissues and plasma were detected using high performance liquid chromatograph and the related enzymes of dopamine (DA) were measured using an enzyme-linked immunosorbent assay. The results indicated that the striatal levels of L-dopa and 3,4-dihydroxyphenylacetic acid (DOPAC) peaked at 1 h and then returned to the normal levels, while the striatal levels of DA were stable within 48 h. In the cortex and hippocampus tissue, L-dopa, DA, DOPAC and homovanillic acid (HVA) levels peaked at 1 h and then returned to normal levels. In the plasma, L-dopa, DA, DOPAC and HVA levels peaked at 1 h. Compared with the control group, L-dopa, DA and HVA levels were higher between 18 and 48 h, whereas the DOPAC level was lower. By contrast, no statistically significant differences were observed in the serotonin (5-HT) levels among the plasma, hippocampus, cortex and striatum. Furthermore, the DA/L-dopa ratio in the brain tissues and plasma increased in the first 5 h, while (DOPAC + HVA)/DA ratios demonstrated a significant reduction. Striatal tyrosine hydroxylase (TH) and aromatic amino acid decarboxylase (AADC) levels were higher compared with the control group; however, catechol-O-methyltransferase (COMT) and monoamine oxidase B levels were reduced. In the rat plasma, TH and COMT peaked at 1 h, while AADC peaked at 5 h. In conclusion, the results of the present study indicate that the co-administration of L-dopa and β-asarone may be used to maintain a stable striatal DA level within 48 h. In addition, this treatment may promote DA generation by AADC and reduce the metabolism of DA by COMT.

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Section: Discussionsupporting

confidence: 45%

Section: Introductionmentioning

confidence: 99%

Dynamic changes of five neurotransmitters and their related enzymes in various rat tissues following β-asarone and levodopa co-administration

Huang

Deng

Fang

et al. 2015

Experimental and Therapeutic Medicine

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“…The intracerebroventricular injection of 3-OMD reduced DA turnover and locomotor activity while it impaired DA uptake in rat striatal membranes and PC12 cells and increased oxidative stress [112]. The behavioral and neurochemical effects of 3-OMD are still present upon sub-chronic intracerebroventricular administration [112,113]. Upon local application on mixed cultured mesencephalic neurons and striatal astrocytes, L-DOPA displayed neuroprotective effects on DA neurons via the involvement of astrocytes.…”

Section: Metabolites Of L-dopamentioning

confidence: 99%

L-DOPA in Parkinson’s Disease: Looking at the “False” Neurotransmitters and Their Meaning

Chagraoui

Boulain

Juvin

et al. 2019

IJMS

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L-3,4-dihydroxyphenylalanine (L-DOPA) has been successfully used in the treatment of Parkinson’s disease (PD) for more than 50 years. It fulfilled the criteria to cross the blood–brain barrier and counteract the biochemical defect of dopamine (DA). It remarkably worked after some adjustments in line with the initial hypothesis, leaving a poor place to the plethora of mechanisms involving other neurotransmitters or mechanisms of action beyond newly synthesized DA itself. Yet, its mechanism of action is far from clear. It involves numerous distinct cell populations and does not mimic the mechanism of action of dopaminergic agonists. L-DOPA-derived DA is mainly released by serotonergic neurons as a false neurotransmitter, and serotonergic neurons are involved in L-DOPA-induced dyskinesia. The brain pattern and magnitude of DA extracellular levels together with this status of false neurotransmitters suggest that the striatal effects of DA via this mechanism would be minimal. Other metabolic products coming from newly formed DA or through the metabolism of L-DOPA itself could be involved. These compounds can be trace amines and derivatives. They could accumulate within the terminals of the remaining monoaminergic neurons. These “false neurotransmitters,” also known for some of them as inducing an “amphetamine-like” mechanism, could reduce the content of biogenic amines in terminals of monoaminergic neurons, thereby impairing the exocytotic process of monoamines including L-DOPA-induced DA extracellular outflow. The aim of this review is to present the mechanism of action of L-DOPA with a specific attention to “false neurotransmission.”

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“…The choice of the doses was based on the results of previous studies [8,42,43]. Ranitidine and cS-induced catalepsy to NCT.…”

Section: Drugs and Dosesmentioning

confidence: 99%

Cyclosomatostatin-induced catalepsy in the aged rat: a response to levodopa, diphenhydramine and nicotine

Ionov¹,

Gorev²,

Pushinskaya³

2018

Current Topics in Pharmacology

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A decrease in somatostatin level is observed in parkinsonian brain. We recently reported that rats given an intracerebroventricular injection of a somatostatin antagonist, cyclosomatostatin, fall into catalepsy; the effect was observed in aged but not young animals. To evaluate the predictive validity of the cyclosomatostatin-induced catalepsy as a model of extrapyramidal disorders, the sensitivity of this catalepsy to clinically effective antiparkinsonian agents was determined. We examined the effects of levodopa and histamine antagonists; also, given an inverse association between Parkinson's disease and tobacco smoking, nicotine was tested. The experiments were conducted using 27-28month-old male Wistar rats. Catalepsy was measured using the bar test. Cyclosomatostatin-induced catalepsy was strongly antagonized by levodopa, which indicates a role for central dopaminergic deficiency in this model. Similarly, histamine H 1receptor antagonist, diphenhydramine, exhibited anticataleptic activity; in contrast, antagonists at H 2and H 3-receptors were without effect. Cataleptic response was inhibited by nicotine; the nicotine sensitivity distinguishes this catalepsy from other models, in particular, from haloperidol-induced catalepsy. Diphenhydramine and nicotine alone only partly suppressed catalepsy; however, coadministration of these drugs almost totally reversed the cataleptogenic effect of cyclosomatostatin. Thus, a similarity between the cyclosomatostatininduced catalepsy and Parkinson's disease with regard to the sensitivity to anti-parkinsonian agents was found. This supports the validity of the model as well as the role of somatostatinergic deficiency in the mechanism of parkinsonian symptoms. Coadministration of diphenhydramine and nicotine appears to be a promising treatment for extrapyramidal disorders in Parkinson's disease.

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Effects of 3-<i>O</i>-Methyldopa, <small>L</small>-3,4-Dihydroxyphenylalanine Metabolite, on Locomotor Activity and Dopamine Turnover in Rats

Cited by 11 publications

References 22 publications

Dynamic changes of five neurotransmitters and their related enzymes in various rat tissues following β-asarone and levodopa co-administration

Dynamic changes of five neurotransmitters and their related enzymes in various rat tissues following β-asarone and levodopa co-administration

L-DOPA in Parkinson’s Disease: Looking at the “False” Neurotransmitters and Their Meaning

Cyclosomatostatin-induced catalepsy in the aged rat: a response to levodopa, diphenhydramine and nicotine

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