• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.108-115
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• 2023

Numerous psychotropic and addictive substances possess structural features similar to those of β-phenethylamine (β-PEA). In this study, we selected 29 β-PEA derivatives and determined their structure-activity relationship (SAR) to their ability to inhibit dopamine (DA) reuptake; conducted docking simulation for two selected compounds; and identified their potential functionals. The compounds were subdivided into arylethylamines, 2-(alkyl amino)-1-arylalkan-1-one derivatives and alkyl 2-phenyl-2-(piperidin-2-yl)acetate derivatives. An aromatic group, alkyl group, and alkylamine derivative were attached to the arylethylamine and 2-(alkyl amino)-1-arylalkan-1-one derivatives. The inhibitory effect of the compounds on dopamine reuptake increased in the order of the compounds substituted with phenyl, thiophenyl, and substituted phenyl groups in the aromatic position; compounds with longer alkyl groups and smaller ring-sized compounds at the alkylamine position showed stronger inhibitory activities. Docking simulation conducted for two compounds, 9 and 28, showed that the (S)-form of compound 9 was more stable than the (R)-form, with a good fit into the binding site covered by helices 1, 3, and 6 of human dopamine transporter (hDAT). In contrast, the (R, S)-configuration of compound 28 was more stable than that of other isomers and was firmly placed in the binding pocket of DAT bound to DA. DA-induced endocytosis of dopamine D₂ receptors was inhibited when they were co-expressed with DAT, which lowered extracellular DA levels, and uninhibited when they were pretreated with compound 9 or 28. In summary, this study revealed critical structural features responsible for the inhibition of DA reuptake and the functional role of DA reuptake inhibitors in regulating D₂ receptor function.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.2
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• pp.118-131
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• 2007

Neurotransmitter imaging with radiopharmaceuticals plays major role for understanding of neurological and psychiatric disorders such as Parkinson's disease and depression. Radiopharmaceuticals for neurotransmitter imaging can be divided to dopamine transporter imaging radiopharmaceuticals and serotonin trnasporter imaging radiopharmaceuticals. Many kinds of new dopamine transporter imaging radiopharmcaeuticals has a tropane ring and they showed different biological properties according to the substituted functional group on tropane ring. After the first clinical trials with $[^{123}I]{\beta}-CIT$, alkyl chain substituent introduced to tropane ring amine to decrease time for imaging acquisition and to increase selectivity. From these results, $[^{123}I]PE2I$, [18F]FE-CNT, $[^{123}I]FP-CIT$ and $[^{18}F]FP-CIT$ were developed and they showed high uptake on the dopamine transporter rich regions and fast peak uptake equilibrium time within 4 hours after injection. $[^{11}C]McN$ 5652 was developed for serotonin trnasporter imaging but this compound showed slow kinetics and high background radioactivity. To overcome these problems, new diarylsulfide backbone derivatives such as ADAM, ODAM, AFM, and DASB were developed. In these candidates, $[^{11}C]AFM$ and $[^{11}C]DASB$ showed high binding affinity to serotonin transporter and fast in vivo kinetics. This paper gives an overview of current status on dopamine and serotonin transporter imaging radiopharmaceuitcals and the development of new lead compounds as potential radiopharmaceuticals by medicinal chemistry.

• YAKHAK HOEJI
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• v.32 no.6
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• pp.402-414
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• 1988

In order to clarify the receptor types and mechanisms underlying the positive inotropic effect of dopamine on the mammalian ventricular myocardium, the action potential, its first derivatives and isometric contraction of the rabbit papillary muscle were recorded using a force transducer and glass capillary microelectrodes filled with 3M KCl. The results were as follows; (1) In normal Tyrode solution, the contractile force was increased and duration of action potential was shortened with increments of dopamine concentration ($10^{-6}-10^{-4}M$). (2) The dose-response curve was markedly shifted to the right by pretreatment with reserpine (5mg/kg i.p., 24hrs prior to the experiment). (3) In 19mM $K^+-Tyrode$ solution, the duration of action potential, maximum rate of rise (V_{max}) of action potential and overshoot were significantly increased with increments of dopamine concentration ($10^{-6}-10^{-4}M$). (4) The inotropic effect of dopamine on the rabbit papillary muscle pretreated with reserpine was antagonized by atenolol ($10^{-6}M$), but not by phentolamine ($3{\times}10^{-6}M$). (5) In rabbit papillary muscle partially depolarized by 19mM $K^+-Tyrode$ solution, slow electrical response (calcium mediated action potential) as well as contraction were restored by dopamine ($10^{-4}M$); this restoration was blocked by calcium antagonists ($3{\times}10^{-5}M$ $LaCl_3{\cdot}6H_2O$, $3{\times}10^{-6}M$ diltiazem) or ${\beta}-adrenoceptor$ antagonist ($3{\times}10^{-6}M$ atenolol), but not affected by ${\alpha}-adrenoceptor$ antagonist ($10^{-5}M$ phentolamine, $3{\times}10^{-6}M$ yohimbine) or vascular dopaminergic receptor antagonist ($10^{-5}M$ haloperidol). The above results may be interpreted as that the positive inotropic effect of dopamine through both direct and indirect action are caused by increase in slow inward current ($Ca^{2+}$ influx into themyocardial cell), and the direct action is mainly due to the stimulation of ${\beta}-adrenoceptors$ in the rabbit papillary muscle.

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.187.1-187.1
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• 2002

• Biomolecules & Therapeutics
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• v.25 no.6
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• pp.578-585
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• 2017

Recently, there has been a rise in the number of amphetamine derivatives that serve as substitutes for controlled substances (e.g. amphetamine and methamphetamine) on the global illegal drug market. These substances are capable of producing rewarding effects similar to their parent drug. In anticipation of the future rise of new and similar psychoactive substances, we designed and synthesized four novel amphetamine derivatives with N-benzyl, N-benzylamphetamine HCl (NBNA) substituent on the amine region, 1,4-dioxane ring, ethylenedioxy-amphetamine HCl (EDA), methyl, para-methylamphetamine HCl (PMEA), and naphthalene, 2-(aminopropyl) naphthalene HCl (2-APN) substituents on the phenyl site. Then, we evaluated their abuse potential in the conditioned place preference (CPP) test in mice and self-administration (SA) test in rats. We also investigated the psychostimulant properties of the novel drugs using the locomotor sensitization test in mice. Moreover, we performed qRT-PCR analyses to explore the effects of the novel drugs on the expression of D1 and D2 dopamine receptor genes in the striatum. NBNA, but not EDA, PMEA, and 2-APN, induced CPP and SA in rodents. None of the test drugs have produced locomotor sensitization. qRT-PCR analyses demonstrated that NBNA increased the expression of striatal D1 dopamine receptor genes. These data indicate that NBNA yields rewarding effects, suggesting potential for abuse. Continual observation for the rise of related substances is thus strongly encouraged.

• Journal of Adhesion and Interface
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• v.19 no.3
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• pp.123-128
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• 2018

As a mussel-inspired surface independent modification chemistry using catecholamine family molecule was suggested on 2007, there are tremendous efforts being done by researchers from around the world to adjust and develop diverse applications using catecholamine family. Accordingly, we will discuss about the novel method to extend catecholamine applications, which is through the functional group substitution of catecholamine molecules.

• Bulletin of the Korean Chemical Society
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• v.34 no.11
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• pp.3467-3470
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• 2013

• The Journal of the Convergence on Culture Technology
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• v.6 no.4
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• pp.761-766
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• 2020

Phenylamine derivatives are substances that have a biochemical action and are widely applied as psychotropic drugs. In particular, with regard to the quantitative analysis of substances such as ephedrine, amphetamine, pentermine, and dopamine, many previous studies such as electrochemical, vacuum ultraviolet method, and gas chromatography have been conducted. However, there have not been many studies on the structural characteristics of molecular units. Therefore, In this study, we used (HyperChem8.0's, HC) semi-empirical PM3 method to calculate the total energy, band gap, electrostatic potential, and net charge of ephedrine, amphetamine, pentamine and dopamine to investigate the chemical properties of each derivative according to the molecular structure change. The results showed that for total energy -43,171.8, -32,9538.3, -36,407.3 and -43,061.2 Kcal/mol, respectively, while for band gaps, 10.16379377, 9.9531666, 9.7878002 and 9.0589282 eV. Also, for electrostatic potentials, 1.301~-0.045, 1.694~0.299, 0.694~-0.158 and 1.587~-0.048 respectively. Finally, looking at the distribution of net charges, the oxygen atoms, nitrogen atoms and carbon atoms were -0.312~-0.242, -0.161~-0.051 and +0.13~-0.12 respectively. These results are expected to lead to chemical action centered on phenyl radicals and oxygen and nitrogen atoms common to phenethylamine derivatives.

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.147.1-147.1
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• 2002

• Journal of Adhesion and Interface
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• v.19 no.1
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• pp.19-29
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• 2018

Polydopamine coating is one of the most straightforward and widely used method for surface modification inspired by adhesiveness of mussel foot protein contributed by co-existence of catechol and amine. This technique has been utilized not only in surface modification but other numerous fields of study as well. For the past decade, the subject of polydopamine has been thoroughly studied since the initial polydopamine research published in 2007, including its chemical structure, coating conditions, and material characteristics. In this study, we report the current trends and progress of polydopamine coating methods, the newly developing areas of polydopamine related research such as using dopamine derivatives and polyphenolic compounds, improvement of various functionalization and application of polydopamine coating, and explain the state of current attempts to discover the chemical mechanism, structure, and properties of polydopamine.