Target Information

Target General Information

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Target ID

T21945 (Former ID: TTDC00304)

Target Name

Norepinephrine transporter (NET)

Synonyms

Solute carrier family 6 member 2; Sodium-dependent noradrenaline transporter; SLC6A2; NET1; NET; NAT1

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Gene Name

SLC6A2

Target Type

Successful target

[1]

Disease

[+] 11 Target-related Diseases

Acute pain [ICD-11: MG31]

Attention deficit hyperactivity disorder [ICD-11: 6A05]

Chronic pain [ICD-11: MG30]

Corneal disease [ICD-11: 9A76-9A78]

Depression [ICD-11: 6A70-6A7Z]

Glaucoma [ICD-11: 9C61]

Migraine [ICD-11: 8A80]

Nicotine use disorder [ICD-11: 6C4A]

Obesity [ICD-11: 5B80-5B81]

Pain [ICD-11: MG30-MG3Z]

Stomach cancer [ICD-11: 2B72]

Function

Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.

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BioChemical Class

Neurotransmitter:sodium symporter

UniProt ID

SC6A2_HUMAN

Sequence

MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGDAQPRETWG
KKIDFLLSVVGFAVDLANVWRFPYLCYKNGGGAFLIPYTLFLIIAGMPLFYMELALGQYN
REGAATVWKICPFFKGVGYAVILIALYVGFYYNVIIAWSLYYLFSSFTLNLPWTDCGHTW
NSPNCTDPKLLNGSVLGNHTKYSKYKFTPAAEFYERGVLHLHESSGIHDIGLPQWQLLLC
LMVVVIVLYFSLWKGVKTSGKVVWITATLPYFVLFVLLVHGVTLPGASNGINAYLHIDFY
RLKEATVWIDAATQIFFSLGAGFGVLIAFASYNKFDNNCYRDALLTSSINCITSFVSGFA
IFSILGYMAHEHKVNIEDVATEGAGLVFILYPEAISTLSGSTFWAVVFFVMLLALGLDSS
MGGMEAVITGLADDFQVLKRHRKLFTFGVTFSTFLLALFCITKGGIYVLTLLDTFAAGTS
ILFAVLMEAIGVSWFYGVDRFSNDIQQMMGFRPGLYWRLCWKFVSPAFLLFVVVVSIINF
KPLTYDDYIFPPWANWVGWGIALSSMVLVPIYVIYKFLSTQGSLWERLAYGITPENEHHL
VAQRDIRQFQLQHWLAI

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3D Structure

Click to Show 3D Structure of This Target

AlphaFold

Drugs and Modes of Action

Top

Approved Drug(s)

[+] 22 Approved Drugs

Amfepramone

Drug Info

Approved

Obesity

[9]

Amoxapine

Drug Info

Approved

Major depressive disorder

[3], [10], [11]

Atomoxetine

Drug Info

Approved

Attention deficit hyperactivity disorder

[12], [13]

Cocaine

Drug Info

Approved

Anaesthesia

[3], [14], [15]

Desipramine

Drug Info

Approved

Attention deficit hyperactivity disorder

[3], [5], [16]

Desvenalfaxine succinate

Drug Info

Approved

Fibromyalgia

[17]

Duloxetine

Drug Info

Approved

Depression

[18], [5]

Imipramine

Drug Info

Approved

Depression

[3], [5], [19]

Iobenguane I-123

Drug Info

Approved

Neuroendocrine cancer

[20]

Levomilnacipran

Drug Info

Approved

Fibromyalgia

[21], [22]

Maprotiline

Drug Info

Approved

Major depressive disorder

[3]

Mazindol

Drug Info

Approved

Obesity

[23], [24]

Milnacipran

Drug Info

Approved

Depression

[25], [26]

Netarsudil

Drug Info

Approved

Open-angle glaucoma

[27]

Phenmetrazine

Drug Info

Approved

Obesity

[28]

Phentermine

Drug Info

Approved

Obesity

[29], [30]

Protriptyline

Drug Info

Approved

Depression

[3], [5], [31]

Reboxetine

Drug Info

Approved

Depression

[32], [5]

Sibutramine

Drug Info

Approved

Obesity

[33], [30]

Tapentadol hydrochloride

Drug Info

Approved

Acute pain

[20]

Trimipramine

Drug Info

Approved

Major depressive disorder

[3]

Venlafaxine

Drug Info

Approved

Depression

[34], [35]

Clinical Trial Drug(s)

[+] 15 Clinical Trial Drugs

Amitifadine

Drug Info

Phase 3

Obesity

[37], [38]

Bicifadine

Drug Info

Phase 3

Neuropathic pain

[39]

Bupropion+naltrexone

Drug Info

Phase 3

Obesity

[40]

Roclatan

Drug Info

Phase 3

Glaucoma/ocular hypertension

[41]

Suronacrine maleate

Drug Info

Phase 3

Cognitive impairment

[42]

18F-LMI-1195

Drug Info

Phase 2

Heart failure

[45]

BLI-1005

Drug Info

Phase 2

Major depressive disorder

[2]

MCT-125

Drug Info

Phase 2

Fatigue

[46]

Metaiodobenzylguanidine I-131

Drug Info

Phase 2

Neuroblastoma

[47]

NS 2359

Drug Info

Phase 2

Cocaine addiction

[2]

Spiroglumide

Drug Info

Phase 2

Stomach disease

[48]

SPN-812

Drug Info

Phase 2

Attention deficit hyperactivity disorder

[49]

TD-9855

Drug Info

Phase 2

Pain

[50]

BL-1021

Drug Info

Phase 1

Pain

[51]

GSK-1360707

Drug Info

Phase 1

Major depressive disorder

[52]

Discontinued Drug(s)

[+] 10 Discontinued Drugs

DOV-216303

Drug Info

Discontinued in Phase 2

Mood disorder

[26]

Esreboxetine

Drug Info

Discontinued in Phase 2

Fibromyalgia

[53]

Manifaxine

Drug Info

Discontinued in Phase 2

Major depressive disorder

[54]

Napitane mesilate

Drug Info

Discontinued in Phase 2

Major depressive disorder

[55]

NS-2389

Drug Info

Discontinued in Phase 2

Major depressive disorder

[56]

R-sibutramine metabolite

Drug Info

Discontinued in Phase 2

Attention deficit hyperactivity disorder

[26]

Radafaxine

Drug Info

Discontinued in Phase 2

Major depressive disorder

[57]

SPD-473

Drug Info

Discontinued in Phase 2

Mood disorder

[58]

NSD-644

Drug Info

Discontinued in Phase 1

Neurological disorder

[59]

RG-7166

Drug Info

Discontinued in Phase 1

Major depressive disorder

[60]

Mode of Action

[+] 6 Modes of Action

Inhibitor

[+] 174 Inhibitor drugs

Amfepramone

Drug Info

[9], [61]

Amoxapine

Drug Info

[62]

Atomoxetine

Drug Info

[63], [64]

Cocaine

Drug Info

[65]

Desipramine

Drug Info

[66]

Desvenalfaxine succinate

Drug Info

[17]

Duloxetine

Drug Info

[67], [68]

Imipramine

Drug Info

[69], [70]

Iobenguane I-123

Drug Info

[71]

Maprotiline

Drug Info

[72]

Milnacipran

Drug Info

[75]

Phenmetrazine

Drug Info

[77]

Phentermine

Drug Info

[78]

Protriptyline

Drug Info

[79]

Reboxetine

Drug Info

[80]

Trimipramine

Drug Info

[81]

Venlafaxine

Drug Info

[1]

Hypericum

Drug Info

[82]

Amitifadine

Drug Info

[71]

Bupropion+naltrexone

Drug Info

[30]

BLI-1005

Drug Info

[2]

MCT-125

Drug Info

[71]

NS 2359

Drug Info

[26], [88]

Spiroglumide

Drug Info

[39]

SPN-812

Drug Info

[2]

GSK-1360707

Drug Info

[90]

DOV-216303

Drug Info

[26]

Radafaxine

Drug Info

[57], [96]

SPD-473

Drug Info

[97]

RG-7166

Drug Info

[99]

((3R,4R)-4-(o-tolyloxy)chroman-3-yl)methanamine

Drug Info

[100]

(+/-)-3-((naphthalen-2-yloxy)methyl)pyrrolidine

Drug Info

[101]

(2S,3S)-2-(m-Tolyl)-3,5,5-trimethylmorpholin-2-ol

Drug Info

[102]

(2S,3S)-2-Phenyl-3,5,5-trimethylmorpholin-2-ol

Drug Info

[102]

(R)-1-((S)-morpholin-2-yl)-1,2-diphenylethanol

Drug Info

[103]

(R)-2-(2-phenyl-2-(piperazin-1-yl)ethyl)phenol

Drug Info

[104]

(R)-6-(pyrrolidin-3-ylmethoxy)-2-naphthonitrile

Drug Info

[101]

(R)-DULOXETINE

Drug Info

[105]

(R)-N-isobutyl-N-(pyrrolidin-3-yl)-2-naphthamide

Drug Info

[106]

(R)-N-isopropyl-N-(pyrrolidin-3-yl)-2-naphthamide

Drug Info

[106]

(R)-Norfluoxetine

Drug Info

[107]

(S)-3-(naphthalen-2-ylmethoxy)pyrrolidine

Drug Info

[101]

(S)-6-(pyrrolidin-3-ylmethoxy)-2-naphthonitrile

Drug Info

[101]

(S)-NORDULOXETINE

Drug Info

[105]

(S)-Norfluoxetine

Drug Info

[107]

1-(1,2-diphenylethyl)piperazine

Drug Info

[108]

1-(1,4-diphenylbutan-2-yl)piperazine

Drug Info

[109]

1-(1-(2-FLUOROPHENYL)-2-(2-(TRIFLUOROMETHOXY)PHENYL)ETHYL)PIPERAZINE (ENANTIOMERIC MIX)

Drug Info

[104]

1-(1-(4-FLUOROPHENYL)-2-(2-(TRIFLUOROMETHOXY)PHENYL)ETHYL)PIPERAZINE (ENANTIOMERIC MIX)

Drug Info

[104]

1-(1-phenyl-2-(2-propoxyphenyl)ethyl)piperazine

Drug Info

[104]

1-(1-phenyl-2-o-tolylethyl)piperazine

Drug Info

[108]

1-(2,3-Dihydro-1H-indol-5-ylmethyl)-propylamine

Drug Info

[110]

1-(2-(2-(DIFLUOROMETHOXY)PHENYL)-1-PHENYLETHYL)PIPERAZINE (ENANTIOMERIC MIX)

Drug Info

[104]

1-(2-(2-bromophenyl)-1-phenylethyl)piperazine

Drug Info

[108]

1-(2-(2-ethylphenyl)-1-phenylethyl)piperazine

Drug Info

[108]

1-(2-(2-fluorobenzyloxy)phenyl)piperazine

Drug Info

[111]

1-(2-(2-methoxyphenyl)-1-phenylethyl)piperazine

Drug Info

[104]

1-(2-(3-chlorophenyl)-1-phenylethyl)piperazine

Drug Info

[108]

1-(2-(3-fluorophenoxy)phenyl)piperazine

Drug Info

[111]

1-(2-(3-methoxyphenyl)-1-phenylethyl)piperazine

Drug Info

[108]

1-(2-(4-fluorophenoxy)phenyl)piperazine

Drug Info

[111]

1-(2-(6-fluoronaphthalen-2-yl)ethyl)piperazine

Drug Info

[101]

1-(2-(phenoxymethyl)phenyl)piperazine

Drug Info

[111]

1-(2-methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one

Drug Info

[112]

1-(2-phenoxyphenyl)piperazine

Drug Info

[111]

1-(3,4-Dichloro-phenyl)-3-diethylamino-indan-5-ol

Drug Info

[113]

1-(3,4-Dichloro-phenyl)-3-methylamino-indan-5-ol

Drug Info

[113]

1-(3-bromophenyl)-2-(tert-butylamino)propan-1-one

Drug Info

[114]

1-(3-chlorophenyl)-2-(dimethylamino)propan-1-one

Drug Info

[114]

1-(3-chlorophenyl)-2-(piperidin-1-yl)propan-1-one

Drug Info

[114]

1-(3-iodophenyl)-2-pyrrolidin-1-yl-pentan-1-one

Drug Info

[112]

1-(3-methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one

Drug Info

[112]

1-(4-bromophenyl)-2-(tert-butylamino)propan-1-one

Drug Info

[114]

1-(4-bromophenyl)-2-pyrrolidin-1-yl-pentan-1-one

Drug Info

[112]

1-(4-fluorophenyl)-2-pyrrolidin-1-yl-pentan-1-one

Drug Info

[112]

1-(4-iodophenyl)-2-pyrrolidin-1-yl-pentan-1-one

Drug Info

[112]

1-(4-nitrophenyl)-2-pyrrolidin-1-yl-pentan-1-one

Drug Info

[112]

1S,2R-milnacipran

Drug Info

[115]

2-((2-iodophenoxy)(phenyl)methyl)morpholine

Drug Info

[116]

2-((3-iodophenyl)(o-tolyloxy)methyl)morpholine

Drug Info

[116]

2-(2'-Aminoethyl)-5-benzyltetrahydrofuran

Drug Info

[117]

2-(2,3-Dihydro-1H-indol-5-yl)-1-methyl-ethylamine

Drug Info

[110]

2-(2-chlorophenoxy)-3-(piperidin-4-yl)pyridine

Drug Info

[118]

2-(2-fluorophenoxy)-3-(piperidin-4-yl)pyridine

Drug Info

[118]

2-(2-methoxyphenoxy)-3-(piperidin-4-yl)pyridine

Drug Info

[118]

2-(2-phenyl-2-(piperazin-1-yl)ethyl)benzonitrile

Drug Info

[108]

2-(Aminomethyl)-5-(1'-naphthethyl)tetrahydrofuran

Drug Info

[117]

2-(Aminomethyl)-5-(2'-naphthyl)tetrahydrofuran

Drug Info

[117]

2-(Aminomethyl)-5-phenethyltetrahydrofuran

Drug Info

[117]

2-(N,N-Diethylamino)-3'-chloropropiophenone

Drug Info

[119]

2-(N-Cyclopentylamino)-3'-bromopropiophenone

Drug Info

[114]

2-(N-Cyclopentylamino)-3'-chloropropiophenone

Drug Info

[119]

2-(N-Cyclopentylamino)-3'-fluoropropiophenone

Drug Info

[114]

2-(N-Cyclopentylamino)-3'-methylpropiophenone

Drug Info

[114]

2-(N-Cyclopropylamino)-3-chloropropiophenone

Drug Info

[119]

2-(N-Pyrrolidinyl)-3'-fluoropropiophenone

Drug Info

[114]

2-(N-Pyrrolidinyl)-3'-methoxypropiophenone

Drug Info

[114]

2-(N-Pyrrolidinyl)-3'-methylpropiophenone

Drug Info

[114]

2-(N-tert-Butylamino)-3',4'-dichloropropiophenone

Drug Info

[119]

100

2-(N-tert-Butylamino)-3'-chloroheptanophenone

Drug Info

[119]

101

2-(N-tert-Butylamino)-3'-chlorooctanophenone

Drug Info

[119]

102

2-(N-tert-Butylamino)propiophenone

Drug Info

[119]

103

2-(tert-butylamino)-1-(3-chlorophenyl)butan-1-one

Drug Info

[114]

104

2-(tert-butylamino)-1-p-tolylpropan-1-one

Drug Info

[114]

105

2-(tert-Butylamino)-3',4'-dichlorobutyrophenone

Drug Info

[119]

106

2-(tert-Butylamino)-3',4'-dichloropentanophenone

Drug Info

[119]

107

2-Amino-1-(4-methylthiophenyl)propane

Drug Info

[120]

108

2-Aminomethyl-5-(p-bromophenyl)tetrahydrofuran

Drug Info

[117]

109

2-Aminomethyl-5-(p-chlorophenyl)tetrahydrofuran

Drug Info

[117]

110

2-Aminomethyl-5-(p-methoxyphenyl)tetrahydrofuran

Drug Info

[117]

111

2-Aminomethyl-5-(p-t-butylphenyl)tetrahydrofuran

Drug Info

[117]

112

2-Aminomethyl-5-(phenyl)tetrahydrofuran

Drug Info

[117]

113

2-phenoxy-3-(piperidin-4-yl)pyridine

Drug Info

[118]

114

2pyrrolidin-1-yl-1-phenylpentan-1-one

Drug Info

[112]

115

3-(1H-indol-1-yl)-N-methyl-3-phenylpropan-1-amine

Drug Info

[121]

116

3-(2-phenyl-2-(piperazin-1-yl)ethyl)benzonitrile

Drug Info

[108]

117

3-(2-phenyl-2-(piperazin-1-yl)ethyl)phenol

Drug Info

[108]

118

3-(3'-furyl)-aniline

Drug Info

[122]

119

3-(piperidin-4-yl)-2-(o-tolyloxy)pyridine

Drug Info

[118]

120

3-p-Tolyl-8-aza-bicyclo[3.2.1]octane

Drug Info

[123]

121

3alpha-(bis-chloro-phenylmethoxy)tropane

Drug Info

[124]

122

4-((naphthalen-2-yloxy)methyl)piperidine

Drug Info

[101]

123

4-(1H-indol-3-yl)-N,N-dimethylcyclohex-3-enamine

Drug Info

[125]

124

4-(2-((3-fluorophenoxy)methyl)phenyl)piperidine

Drug Info

[111]

125

4-(2-(2-fluoro-5-methylphenoxy)phenyl)piperidine

Drug Info

[111]

126

4-(2-(2-fluorobenzyloxy)phenyl)piperidine

Drug Info

[111]

127

4-(2-(3-chlorophenoxy)phenyl)piperidine

Drug Info

[111]

128

4-(2-(3-fluorophenoxy)-4-methylphenyl)piperidine

Drug Info

[111]

129

4-(2-(3-fluorophenoxy)phenyl)piperidine

Drug Info

[111]

130

4-(2-(4-fluorobenzyloxy)phenyl)piperidine

Drug Info

[111]

131

4-(2-(4-fluorophenoxy)-4-methylphenyl)piperidine

Drug Info

[111]

132

4-(2-(4-fluorophenoxy)phenyl)piperidine

Drug Info

[111]

133

4-(2-(benzyloxy)-3-fluorophenyl)piperidine

Drug Info

[111]

134

4-(2-(benzyloxy)-6-fluorophenyl)piperidine

Drug Info

[111]

135

4-(2-(benzyloxy)phenyl)piperidine

Drug Info

[111]

136

4-(2-fluoro-6-(3-fluorophenoxy)phenyl)piperidine

Drug Info

[111]

137

4-(2-fluoro-6-(4-fluorophenoxy)phenyl)piperidine

Drug Info

[111]

138

4-(2-fluoro-6-phenoxyphenyl)piperidine

Drug Info

[111]

139

4-(2-phenoxyphenyl)piperidine

Drug Info

[111]

140

4-(3'-furyl)-aniline

Drug Info

[122]

141

4-(3-fluoro-2-phenoxyphenyl)piperidine

Drug Info

[111]

142

4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one

Drug Info

[126]

143

6-(piperidin-4-ylmethoxy)-2-naphthonitrile

Drug Info

[101]

144

7-(piperidin-4-ylmethoxy)-2-naphthonitrile

Drug Info

[101]

145

8-Methyl-3-p-tolyl-8-aza-bicyclo[3.2.1]octane

Drug Info

[123]

146

Biphenyl-2-ylmethyl-(S)-pyrrolidin-3-yl-amine

Drug Info

[127]

147

Cis-3-phenoxy-2,3-dihydro-1H-inden-1-amine

Drug Info

[128]

148

D-211A

Drug Info

[129]

149

D-211B

Drug Info

[129]

150

D-254C

Drug Info

[129]

151

D-257A

Drug Info

[129]

152

D-257C

Drug Info

[129]

153

Isobutyl-(4-methyl-benzyl)-piperidin-4-yl-amine

Drug Info

[130]

154

KF-A5

Drug Info

[131]

155

MDL-28618

Drug Info

[100]

156

METHYLENEDIOXYAMPHETAMINE

Drug Info

[132]

157

METHYLENEDIOXYMETHAMPHETAMINE

Drug Info

[120], [133]

158

N-(2-oxazolemethyl)milnacipran

Drug Info

[135]

159

N-benzyl-N-isobutylpiperidin-4-amine

Drug Info

[130]

160

N-desalkylquetiapine

Drug Info

[136]

161

NISOXETINE

Drug Info

[137]

162

norzotepine

Drug Info

[138]

163

Para-chloroamphetamine

Drug Info

[120]

164

PF-18298

Drug Info

[104]

165

PF-3409409

Drug Info

[139]

166

PTI-601

Drug Info

[71]

167

PYROVALERONE

Drug Info

[112]

168

S-34324

Drug Info

[140]

169

S33005

Drug Info

[141]

170

WAY-256805

Drug Info

[142]

171

WIN-35066-2

Drug Info

[143]

172

[3-(3,4-Dichloro-phenyl)-indan-1-yl]-methyl-amine

Drug Info

[113]

173

[3H]nisoxetine

Drug Info

[71]

174

[3H]WIN35428

Drug Info

[144]

Modulator

[+] 16 Modulator drugs

Levomilnacipran

Drug Info

[22]

Mazindol

Drug Info

[73], [74]

Netarsudil

Drug Info

[76]

Sibutramine

Drug Info

[74]

Tapentadol hydrochloride

Drug Info

[20]

Bicifadine

Drug Info

[83]

Roclatan

Drug Info

[84]

Suronacrine maleate

Drug Info

[85]

Metaiodobenzylguanidine I-131

Drug Info

[87]

TD-9855

Drug Info

[50]

BL-1021

Drug Info

[89]

Manifaxine

Drug Info

[92]

Napitane mesilate

Drug Info

[93]

NS-2389

Drug Info

[94]

R-sibutramine metabolite

Drug Info

[95]

MMDA

Drug Info

[134]

Enhancer

[+] 1 Enhancer drugs

18F-LMI-1195

Drug Info

[86]

Blocker

[+] 1 Blocker drugs

Esreboxetine

Drug Info

[91]

Activator

[+] 1 Activator drugs

NSD-644

Drug Info

[98]

Agonist

[+] 1 Agonist drugs

TQ-1017

Drug Info

[3]

Cell-based Target Expression Variations

Top

Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Human Similarity Proteins Human Pathway Affiliation

Different Human System Profiles of Target

Top

Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Human Similarity Proteins

Human Pathway Affiliation

There is no similarity protein (E value < 0.005) for this target

KEGG Pathway	Pathway ID	Affiliated Target	Pathway Map
Synaptic vesicle cycle	hsa04721	Affiliated Target
Class: Organismal Systems => Nervous system	Pathway Hierarchy

Chemical Structure based Activity Landscape of Target

Top

Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

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Co-Targets

Co-Targets Info

Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

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Panther Pathway

[+] 1 Panther Pathways

Adrenaline and noradrenaline biosynthesis

Reactome

[+] 1 Reactome Pathways

Na+/Cl- dependent neurotransmitter transporters

WikiPathways

[+] 3 WikiPathways

Monoamine Transport

NRF2 pathway

Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 1

Clinically relevant drug interactions with new generation antidepressants and antipsychotics. Ther Umsch. 2009 Jun;66(6):485-92.

REF 2

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 3

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

REF 4

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 200).

REF 5

Emerging treatments for depression. Expert Opin Pharmacother. 2006 Dec;7(17):2323-39.

REF 6

The Diversion of Ultram, Ultracet, and generic tramadol HCL. J Addict Dis. 2006;25(2):53-8.

REF 7

REF 8

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 018337.

REF 9

Pharmacotherapy for obesity. Drugs. 2005;65(10):1391-418.

REF 10

REF 11

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 072688.

REF 12

REF 13

Anti-obesity drugs and neural circuits of feeding. Trends Pharmacol Sci. 2008 Apr;29(4):208-17.

REF 14

REF 15

Drug information of Cocaine, 2008. eduDrugs.

REF 16

REF 17

Emerging therapies for fibromyalgia. Expert Opin Emerg Drugs. 2008 Mar;13(1):53-62.

REF 18

REF 19

REF 20

2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.

REF 21

REF 22

Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.

REF 23

REF 24

Use of sibutramine and other noradrenergic and serotonergic drugs in the management of obesity. Endocrine. 2000 Oct;13(2):193-9.

REF 25

REF 26

Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92.

REF 27

2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.

REF 28

Drug information of Phenmetrazine, 2008. eduDrugs.

REF 29

REF 30

Anti-obesity drugs. Expert Opin Pharmacother. 2008 Jun;9(8):1339-50.

REF 31

REF 32

REF 33

REF 34

REF 35

Desvenlafaxine in the treatment of major depressive disorder. Neuropsychiatr Dis Treat. 2009;5:127-36.

REF 36

ClinicalTrials.gov (NCT04786990) Open-Label Study of SPN-812 Administered With Psychostimulants in Children and Adolescents With ADHD (ADHD). U.S. National Institutes of Health.

REF 37

DOV 216,303, a "triple" reuptake inhibitor: safety, tolerability, and pharmacokinetic profile. J Clin Pharmacol. 2004 Dec;44(12):1360-7.

REF 38

Preclinical and clinical pharmacology of DOV 216,303, a "triple" reuptake inhibitor. CNS Drug Rev. 2006 Summer;12(2):123-34.

REF 39

Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.

REF 40

A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring). 2013 May;21(5):935-43.

REF 41

ClinicalTrials.gov (NCT02558400) Double-masked Study of PG324 Ophthalmic Solution in Patients With Glaucoma or Ocular Hypertension.

REF 42

Handbook of Dementing Illnesses, Morris John. Page(570).

REF 43

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021315)

REF 44

ClinicalTrials.gov (NCT02699086) A Study of PDC-1421 Treatment in Adult Patients With Attention-Deficit Hyperactivity Disorder (ADHD). U.S. National Institutes of Health.

REF 45

ClinicalTrials.gov (NCT01085175) Trial to Determine Imaging Parameters of LMI1195 in Heart Failure Patients at Low and High Risk of Defibrillator Firing. U.S. National Institutes of Health.

REF 46

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022855)

REF 47

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004852)

REF 48

Progress medicinal chem PMC37H. Page(48).

REF 49

ClinicalTrials.gov (NCT01107496) A Phase I/IIa, Randomized, Double-Blind, Multicenter, Placebo-Controlled, Parallel-Group Study of the Safety, and Efficacy of SPN-812V in Adults With Attention Deficit Hyperactivity Disorder (ADHD). U.S. National Institutes of Health.

REF 50

Preclinical to clinical translation of CNS transporter occupancy of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor. Int J Neuropsychopharmacol. 2014 Dec 13;18(2). pii: pyu027.

REF 51

ClinicalTrials.gov (NCT01121380) A Study Intended to Evaluate Safety, Tolerability and Pharmacokinetics (PK) Parameters of BL-1021. U.S. National Institutes of Health.

REF 52

ClinicalTrials.gov (NCT01153802) An Open Label Positron Emission Tomography Study in Healthy Male Subjects to Investigate Brain DAT and SERT Occupancy,Pharmacokinetics and Safety of Single Oral Dosesof GSK1360707, Using 11C- PE2I and 11C-DASB as PET Ligands. U.S. National Institutes of Health.

REF 53

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800040151)

REF 54

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006906)

REF 55

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005107)

REF 56

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009012)

REF 57

Emerging drugs for bipolar disorder. Expert Opin Emerg Drugs. 2006 Nov;11(4):621-34.

REF 58

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010517)

REF 59

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027571)

REF 60

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031598)

REF 61

Phentermine and anaesthesia. Anaesth Intensive Care. 2005 Aug;33(4):525-7.

REF 62

Effects of acute and chronic treatment with amoxapine and cericlamine on the sleep-wakefulness cycle in the rat. Neuropharmacology. 1994 Aug;33(8):1017-25.

REF 63

Atomoxetine reverses attentional deficits produced by noradrenergic deafferentation of medial prefrontal cortex. Psychopharmacology (Berl). 2008 Sep;200(1):39-50.

REF 64

New drugs for the treatment of attention-deficit/hyperactivity disorder. Expert Opin Emerg Drugs. 2004 Nov;9(2):293-302.

REF 65

Differential involvement of the norepinephrine, serotonin and dopamine reuptake transporter proteins in cocaine-induced taste aversion. Pharmacol Biochem Behav. 2009 Jul;93(1):75-81.

REF 66

Augmentation effect of combination therapy of aripiprazole and antidepressants on forced swimming test in mice. Psychopharmacology (Berl). 2009 Sep;206(1):97-107.

REF 67

Multi-target therapeutics: when the whole is greater than the sum of the parts. Drug Discov Today. 2007 Jan;12(1-2):34-42.

REF 68

Duloxetine for the treatment of generalized anxiety disorder: a review. Neuropsychiatr Dis Treat. 2009;5:23-31.

REF 69

Invivo antioxidant status: a putative target of antidepressant action. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Mar 17;33(2):220-8.

REF 70

Pharmacological profile of neuroleptics at human monoamine transporters. Eur J Pharmacol. 1999 Mar 5;368(2-3):277-83.

REF 71

REF 72

Effect of pharmacologically selective antidepressants on serotonin uptake in rat platelets. Gen Physiol Biophys. 2005 Mar;24(1):113-28.

REF 73

Binding of [3H]mazindol to cardiac norepinephrine transporters: kinetic and equilibrium studies. Naunyn Schmiedebergs Arch Pharmacol. 2004 Jul;370(1):9-16.

REF 74

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

REF 75

Milnacipran: beyond a role of antidepressant. Clin Neuropharmacol. 2009 Nov-Dec;32(6):355-63.

REF 76

Effect of 0.04% AR-13324, a ROCK, and norepinephrine transporter inhibitor, on aqueous humor dynamics in normotensive monkey eyes. J Glaucoma. 2015 Jan;24(1):51-4.

REF 77

Interaction of the anorectic medication, phendimetrazine, and its metabolites with monoamine transporters in rat brain. Eur J Pharmacol. 2002 Jun 28;447(1):51-7.

REF 78

Novel anti-obesity drugs. Expert Opin Investig Drugs. 2000 Jun;9(6):1317-26.

REF 79

Analgesic properties of intrathecally administered heterocyclic antidepressants. Pain. 1987 Mar;28(3):343-55.

REF 80

Reboxetine: the first selective noradrenaline re-uptake inhibitor. Expert Opin Pharmacother. 2000 May;1(4):771-82.

REF 81

Antidepressants suppress production of the Th1 cytokine interferon-gamma, independent of monoamine transporter blockade. Eur Neuropsychopharmacol. 2006 Oct;16(7):481-90.

REF 82

The experimental and clinical pharmacology of St John's Wort (Hypericum perforatum L.). Mol Psychiatry. 1999 Jul;4(4):333-8.

REF 83

Preclinical Evaluation of the Abuse Potential of the Analgesic Bicifadine

REF 84

Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.

REF 85

Potential clinical use of an adrenergic/cholinergic agent (HP 128) in the treatment of Alzheimer's disease. Ann N Y Acad Sci. 1991;640:263-7.

REF 86

Assessment of the 18F-labeled PET tracer LMI1195 for imaging norepinephrine handling in rat hearts. J Nucl Med. 2013 Jul;54(7):1142-6.

REF 87

Imaging the norepinephrine transporter in neuroblastoma: a comparison of [18F]-MFBG and 123I-MIBG. Clin Cancer Res. 2014 Apr 15;20(8):2182-91.

REF 88

Emerging drugs for attention-deficit/hyperactivity disorder. Expert Opin Emerg Drugs. 2007 Sep;12(3):423-34.

REF 89

Company report (BioLineRx)

REF 90

Monoamine transporter occupancy of a novel triple reuptake inhibitor in baboons and humans using positron emission tomography. J Pharmacol Exp Ther. 2013 Aug;346(2):311-7.

REF 91

Pfizer. Product Development Pipeline. March 31 2009.

REF 92

Pharmacogenetics and obesity: common gene variants influence weight loss response of the norepinephrine/dopamine transporter inhibitor GW320659 in obese subjects. Pharmacogenet Genomics. 2005 Dec;15(12):883-9.

REF 93

Enhancing central noradrenergic function in depression: is there still a place for a new antidepressant

REF 94

Clinical pipeline report, company report or official report of Neurosearch.

REF 95

Monoamine reuptake site occupancy of sibutramine: Relationship to antidepressant-like and thermogenic effects in rats.Eur J Pharmacol.2014 Aug 15;737:47-56.

REF 96

Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.

REF 97

Dopamine uptake inhibitor-induced rotation in 6-hydroxydopamine-lesioned rats involves both D1 and D2 receptors but is modulated through 5-hydroxyt... J Pharmacol Exp Ther. 2005 Mar;312(3):1124-31.

REF 98

Clinical pipeline report, company report or official report of Neurosearch.

REF 99

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031598)

REF 100

Synthesis and structure-activity relationships of selective norepinephrine reuptake inhibitors (sNRI) with a heterocyclic ring constraint. Bioorg Med Chem Lett. 2008 Aug 15;18(16):4495-8.

REF 101

Design and optimization of selective serotonin re-uptake inhibitors with high synthetic accessibility. Part 1. Bioorg Med Chem Lett. 2009 Apr 15;19(8):2329-32.

REF 102

Synthesis and characterization of in vitro and in vivo profiles of hydroxybupropion analogues: aids to smoking cessation. J Med Chem. 2010 Jun 24;53(12):4731-48.

REF 103

Discovery of novel and selective tertiary alcohol containing inhibitors of the norepinephrine transporter. Bioorg Med Chem Lett. 2006 Apr 1;16(7):2022-5.

REF 104

Second generation N-(1,2-diphenylethyl)piperazines as dual serotonin and noradrenaline reuptake inhibitors: improving metabolic stability and reduc... Bioorg Med Chem Lett. 2010 Jun 15;20(12):3788-92.

REF 105

Inhibition of serotonin and norepinephrine reuptake and inhibition of phosphodiesterase by multi-target inhibitors as potential agents for depression. Bioorg Med Chem. 2009 Oct 1;17(19):6890-7.

REF 106

Bioorg Med Chem Lett. 2009 Oct 15;19(20):5893-7. Epub 2009 Aug 21.Design and optimisation of selective serotonin re-uptake inhibitors with high synthetic accessibility: part 2.

REF 107

Stereoselective inhibition of serotonin re-uptake and phosphodiesterase by dual inhibitors as potential agents for depression. Bioorg Med Chem. 2009 Jan 1;17(1):337-43.

REF 108

N-(1,2-diphenylethyl)piperazines: a new class of dual serotonin/noradrenaline reuptake inhibitor. Bioorg Med Chem Lett. 2006 Aug 15;16(16):4345-8.

REF 109

Structure-activity relationships of N-substituted piperazine amine reuptake inhibitors. Bioorg Med Chem Lett. 2006 Aug 15;16(16):4349-53.

REF 110

Selective monoamine oxidase inhibitors. 3. Cyclic compounds related to 4-aminophenethylamine. Preparation and neuron-selective action of some 5-(2-... J Med Chem. 1986 Aug;29(8):1406-12.

REF 111

Discovery and pharmacological characterization of aryl piperazine and piperidine ethers as dual acting norepinephrine reuptake inhibitors and 5-HT1... Bioorg Med Chem Lett. 2009 Dec 1;19(23):6604-7.

REF 112

1-(4-Methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one (Pyrovalerone) analogues: a promising class of monoamine uptake inhibitors. J Med Chem. 2006 Feb 23;49(4):1420-32.

REF 113

Synthesis and pharmacological evaluation of 3-(3,4-dichlorophenyl)-1-indanamine derivatives as nonselective ligands for biogenic amine transporters. J Med Chem. 2004 May 6;47(10):2624-34.

REF 114

Synthesis and biological evaluation of bupropion analogues as potential pharmacotherapies for smoking cessation. J Med Chem. 2010 Mar 11;53(5):2204-14.

REF 115

Characterization of thien-2-yl 1S,2R-milnacipran analogues as potent norepinephrine/serotonin transporter inhibitors for the treatment of neuropath... J Med Chem. 2008 Nov 27;51(22):7265-72.

REF 116

Development of SPECT imaging agents for the norepinephrine transporters: [123I]INER. Bioorg Med Chem Lett. 2007 Jan 15;17(2):533-7.

REF 117

2,5-Disubstituted tetrahydrofurans as selective serotonin re-uptake inhibitors. Bioorg Med Chem. 2009 Mar 1;17(5):2047-68.

REF 118

Design, synthesis, and pharmacological evaluation of phenoxy pyridyl derivatives as dual norepinephrine reuptake inhibitors and 5-HT1A partial agon... Bioorg Med Chem Lett. 2010 Feb 1;20(3):1114-7.

REF 119

Synthesis and biological evaluation of bupropion analogues as potential pharmacotherapies for cocaine addiction. J Med Chem. 2009 Nov 12;52(21):6768-81.

REF 120

Synthesis and serotonin transporter activity of sulphur-substituted alpha-alkyl phenethylamines as a new class of anticancer agents. Eur J Med Chem. 2009 Dec;44(12):4862-88.

REF 121

Synthesis and activity of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors. Bioorg Med Chem Lett. 2008 Dec 1;18(23):6067-70.

REF 122

Designing active template molecules by combining computational de novo design and human chemist's expertise. J Med Chem. 2007 Apr 19;50(8):1925-32.

REF 123

3alpha-(4-Substituted phenyl)nortropane-2beta-carboxylic acid methyl esters show selective binding at the norepinephrine transporter. Bioorg Med Chem Lett. 2000 Nov 6;10(21):2445-7.

REF 124

Structure-activity relationship studies on a novel series of (S)-2beta-substituted 3alpha-[bis(4-fluoro- or 4-chlorophenyl)methoxy]tropane analogue... J Med Chem. 2006 Oct 19;49(21):6391-9.

REF 125

Conformationally restricted homotryptamines 3. Indole tetrahydropyridines and cyclohexenylamines as selective serotonin reuptake inhibitors. Bioorg Med Chem Lett. 2007 Jun 1;17(11):3099-104.

REF 126

Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 rec... J Med Chem. 2010 Sep 9;53(17):6386-97.

REF 127

Derivatives of (3S)-N-(biphenyl-2-ylmethyl)pyrrolidin-3-amine as selective noradrenaline reuptake inhibitors: Reducing P-gp mediated efflux by modu... Bioorg Med Chem Lett. 2008 Aug 1;18(15):4355-9.

REF 128

Discovery of a potent, selective, and less flexible selective norepinephrine reuptake inhibitor (sNRI). Bioorg Med Chem Lett. 2008 Jul 15;18(14):4224-7.

REF 129

Further structural optimization of cis-(6-benzhydryl-piperidin-3-yl)-benzylamine and 1,4-diazabicyclo[3.3.1]nonane derivatives by introducing an ex... Bioorg Med Chem. 2008 Mar 15;16(6):2769-78.

REF 130

N-Alkyl-N-arylmethylpiperidin-4-amines: novel dual inhibitors of serotonin and norepinephrine reuptake. Bioorg Med Chem Lett. 2006 May 15;16(10):2714-8.

REF 131

Design, synthesis, and evaluation of 10-N-substituted acridones as novel chemosensitizers in Plasmodium falciparum. Antimicrob Agents Chemother. 2007 Nov;51(11):4133-40.

REF 132

Synthesis and in vitro toxicity of 4-MTA, its characteristic clandestine synthesis byproducts and related sulfur substituted alpha-alkylthioampheta... Bioorg Med Chem. 2010 Jun 1;18(11):4009-31.

REF 133

The origin of MDMA (ecstasy) revisited: the true story reconstructed from the original documents. Addiction. 2006 Sep;101(9):1241-5.

REF 134

How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

REF 135

Studies on the SAR and pharmacophore of milnacipran derivatives as monoamine transporter inhibitors. Bioorg Med Chem Lett. 2008 Feb 15;18(4):1346-9.

REF 136

N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant ... Neuropsychopharmacology. 2008 Sep;33(10):2303-12.

REF 137

Synthesis and activity of 1-(3-amino-1-phenylpropyl)indolin-2-ones: a new class of selective norepinephrine reuptake inhibitors. Bioorg Med Chem Lett. 2008 Sep 15;18(18):4929-31.

REF 138

Norzotepine, a major metabolite of zotepine, exerts atypical antipsychotic-like and antidepressant-like actions through its potent inhibition of norepinephrine reuptake. J Pharmacol Exp Ther. 2010 Jun;333(3):772-81.

REF 139

Design, synthesis and evaluation of N-[(3S)-pyrrolidin-3-yl]benzamides as selective noradrenaline reuptake inhibitors: CNS penetration in a more po... Bioorg Med Chem Lett. 2009 Aug 15;19(16):4579-83.

REF 140

Discovery of a new series of centrally active tricyclic isoxazoles combining serotonin (5-HT) reuptake inhibition with alpha2-adrenoceptor blocking... J Med Chem. 2005 Mar 24;48(6):2054-71.

REF 141

Serotonin reuptake inhibitors: the corner stone in treatment of depression for half a century--a medicinal chemistry survey. Curr Top Med Chem. 2006;6(17):1801-23.

REF 142

Structure-activity relationships of the cycloalkanol ethylamine scaffold: discovery of selective norepinephrine reuptake inhibitors. J Med Chem. 2008 Jul 10;51(13):4038-49.

REF 143

Monoamine transporter binding, locomotor activity, and drug discrimination properties of 3-(4-substituted-phenyl)tropane-2-carboxylic acid methyl e... J Med Chem. 2004 Dec 2;47(25):6401-9.

REF 144

3 alpha-(4'-substituted phenyl)tropane-2 beta-carboxylic acid methyl esters: novel ligands with high affinity and selectivity at the dopamine trans... J Med Chem. 1996 Oct 11;39(21):4139-41.

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