Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0030567 (
Parkinson's disease
)
63,064
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Monoamine oxidase type B
inhibitors act in
Parkinson's disease
(PD) via potentiation of dopamine, but may also have neuroprotective effects by reducing oxidative damage. Oxidative damage is also a feature of environmental toxins, including pesticides, that are an established risk factor for PD. Another risk factor is low circulating uric acid (UA), which may relate to UA being the major endogenous antioxidant in the human body. We have undertaken a study of 192 initial admissions for PD in a general hospital neurology department in a partly rural region of Southern China to determine if there is an increased rate of PD in agricultural workers who have a high risk of exposure to pesticides, and how it may relate to deficits in UA. We found a disproportionately high number of agricultural workers admitted with PD (66.7% vs. 54.3% of all neurology admissions) and that PD subjects have a substantial reduction in UA. This is further reduced in agricultural workers and thus may contribute to the increased vulnerability of this group to PD.
...
PMID:Agricultural work and reduced circulating uric acid are both associated with initial hospital admission for Parkinson's disease. 3183 5
Dual target ligands are a promising concept for the treatment of
Parkinson's disease
(PD). A combination of monoamine oxidase B (
MAO B
) inhibition with histamine H
3
receptor (H
3
R) antagonism could have positive effects on dopamine regulation. Thus, a series of twenty-seven 4-
tert
-butylphenoxyalkoxyamines were designed as potential dual-target ligands for PD based on the structure of 1-(3-(4-
tert
-butylphenoxy)propyl)piperidine (
DL76
). Probed modifications included the introduction of different cyclic amines and elongation of the alkyl chain. Synthesized compounds were investigated for human H
3
R (hH
3
R) affinity and human
MAO B
(hMAO B) inhibitory activity. Most compounds showed good hH
3
R affinities with K
i
values below 400 nM, and some of them showed potent inhibitory activity for hMAO B with IC
50
values below 50 nM. However, the most balanced activity against both biological targets showed
DL76
(hH
3
R: K
i
= 38 nM and hMAO B: IC
50
= 48 nM). Thus,
DL76
was chosen for further studies, revealing the nontoxic nature of
DL76
in HEK293 and neuroblastoma SH-SY5Ycells. However, no neuroprotective effect was observed for
DL76
in hydrogen peroxide-treated neuroblastoma SH-SY5Y cells. Furthermore, in vivo studies showed antiparkinsonian activity of
DL76
in haloperidol-induced catalepsy (Cross Leg Position Test) at a dose of 50 mg/kg body weight.
...
PMID:Dual Target Ligands with 4-
tert-
Butylphenoxy Scaffold as Histamine H
3
Receptor Antagonists and Monoamine Oxidase B Inhibitors. 3240 4
<< Previous
1
2
3
4
5
6
7
8
