Page last updated: 2024-12-10

nafadotride

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

nafadotride: structure given in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

nafadotride : A naphthalenecarboxamide resulting from the formal condensation of the carboxylic acid group of 4-cyano-1-methoxynaphthalene-2-carboxylic acid with the primary amino group of 1-(1-butylpyrrolidin-2-yl]methanamine. It is a highly potent, competitive, preferential dopamine D3 receptor antagonist, centrally active upon systemic administration. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID3408722
CHEMBL ID286252
CHEBI ID64191
SCHEMBL ID635866
MeSH IDM0255741

Synonyms (37)

Synonym
HMS3267P15
HMS3394A15
BRD-A71262238-001-04-3
gtpl44
MLS001424218
nafadotride
MLS000758952
smr000466292
n-[(1-butylpyrrolidin-2-yl)methyl]-4-cyano-1-methoxynaphthalene-2-carboxamide
149649-22-9
HMS2052A15
4-cyano-1-methoxy-naphthalene-2-carboxylic acid (1-butyl-pyrrolidin-2-ylmethyl)-amide
bdbm50133923
chebi:64191 ,
CHEMBL286252 ,
L000428
HMS2232B11
CCG-101119
FT-0643448
n-[(1-butyl-2-pyrrolidinyl)methyl]-4-cyano-1-methoxy-2-naphthalenecarboxamide
(+-)-nafadotride
HMS3370D02
SCHEMBL635866
NC00369
DTXSID1042603
AKOS024257976
SR-01000597572-1
sr-01000597572
A1-01951
J-008605
n-((1-butylpyrrolidin-2-yl)methyl)-4-cyano-1-methoxy-2-naphthamide
HMS3678K11
n-((1-butyl-2-pyrrolidinyl)methyl)-4-cyano-1-methoxy-2-naphthalenecarboxamide
BCP27779
HMS3414K11
Q6958145
2-naphthalenecarboxamide, n-[(1-butyl-2-pyrrolidinyl)methyl]-4-cyano-1-methoxy-

Research Excerpts

Effects

ExcerptReferenceRelevance
"Nafadotride has been proposed as a selective antagonist for the D3 dopamine receptor. "( In vivo occupancy of D2 dopamine receptors by nafadotride.
Levant, B; Vansell, NR, 1997
)
2

Actions

ExcerptReferenceRelevance
"l-Nafadotride displays iow, micromolar affinity at dopamine D1 and D4 receptors and negligible apparent affinity at various other receptors."( Nafadotride, a potent preferential dopamine D3 receptor antagonist, activates locomotion in rodents.
Costentin, J; Garrido, F; Griffon, N; Launay, C; Mann, A; Sautel, F; Schoenfelder, A; Schwartz, JC; Simon, P; Sokoloff, P, 1995
)
2.29

Dosage Studied

ExcerptRelevanceReference
" l-Nafadotride displaces in vivo N-[3H]propylnorapomorphine accumulation at lower dosage and for longer periods in limbic structures, containing both dopamine D2 and D3 receptors than in the stratum, containing dopamine D2 receptor only."( Nafadotride, a potent preferential dopamine D3 receptor antagonist, activates locomotion in rodents.
Costentin, J; Garrido, F; Griffon, N; Launay, C; Mann, A; Sautel, F; Schoenfelder, A; Schwartz, JC; Simon, P; Sokoloff, P, 1995
)
2.36
" The present study was designed to determine the extent to which D2/3 receptor activation and blockade can modulate morphine-induced locomotion using a novel cumulative dosing procedure in Swiss-Webster mice."( The modulatory actions of dopamine D2/3 agonists and antagonists on the locomotor-activating effects of morphine and caffeine in mice.
Beardsley, PM; Cook, CD, 2003
)
0.32
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (1)

RoleDescription
dopaminergic antagonistA drug that binds to but does not activate dopamine receptors, thereby blocking the actions of dopamine or exogenous agonists.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (5)

ClassDescription
tertiary amino compoundA compound formally derived from ammonia by replacing three hydrogen atoms by organyl groups.
nitrileA compound having the structure RC#N; thus a C-substituted derivative of hydrocyanic acid, HC#N. In systematic nomenclature, the suffix nitrile denotes the triply bound #N atom, not the carbon atom attached to it.
naphthalenecarboxamideAny member of the class of naphthalenes in which the naphthalene ring is directly attached to the carbonyl carbon of a carboxamide group.
pyrrolidinesAny of a class of heterocyclic amines having a saturated five-membered ring.
aromatic etherAny ether in which the oxygen is attached to at least one aryl substituent.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (4)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, 2-oxoglutarate OxygenaseHomo sapiens (human)Potency39.81070.177814.390939.8107AID2147
mitogen-activated protein kinase 1Homo sapiens (human)Potency15.84890.039816.784239.8107AID1454
muscleblind-like protein 1 isoform 1Homo sapiens (human)Potency0.89130.00419.962528.1838AID2675
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
D(3) dopamine receptorHomo sapiens (human)Ki0.00050.00000.602010.0000AID65133; AID65783
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (40)

Processvia Protein(s)Taxonomy
response to ethanolD(3) dopamine receptorHomo sapiens (human)
synaptic transmission, dopaminergicD(3) dopamine receptorHomo sapiens (human)
G protein-coupled receptor internalizationD(3) dopamine receptorHomo sapiens (human)
intracellular calcium ion homeostasisD(3) dopamine receptorHomo sapiens (human)
G protein-coupled receptor signaling pathwayD(3) dopamine receptorHomo sapiens (human)
adenylate cyclase-activating dopamine receptor signaling pathwayD(3) dopamine receptorHomo sapiens (human)
adenylate cyclase-inhibiting dopamine receptor signaling pathwayD(3) dopamine receptorHomo sapiens (human)
learning or memoryD(3) dopamine receptorHomo sapiens (human)
learningD(3) dopamine receptorHomo sapiens (human)
locomotory behaviorD(3) dopamine receptorHomo sapiens (human)
visual learningD(3) dopamine receptorHomo sapiens (human)
response to xenobiotic stimulusD(3) dopamine receptorHomo sapiens (human)
regulation of dopamine secretionD(3) dopamine receptorHomo sapiens (human)
positive regulation of cytokinesisD(3) dopamine receptorHomo sapiens (human)
circadian regulation of gene expressionD(3) dopamine receptorHomo sapiens (human)
response to histamineD(3) dopamine receptorHomo sapiens (human)
social behaviorD(3) dopamine receptorHomo sapiens (human)
response to cocaineD(3) dopamine receptorHomo sapiens (human)
dopamine metabolic processD(3) dopamine receptorHomo sapiens (human)
response to morphineD(3) dopamine receptorHomo sapiens (human)
negative regulation of blood pressureD(3) dopamine receptorHomo sapiens (human)
positive regulation of mitotic nuclear divisionD(3) dopamine receptorHomo sapiens (human)
acid secretionD(3) dopamine receptorHomo sapiens (human)
behavioral response to cocaineD(3) dopamine receptorHomo sapiens (human)
negative regulation of oligodendrocyte differentiationD(3) dopamine receptorHomo sapiens (human)
arachidonic acid secretionD(3) dopamine receptorHomo sapiens (human)
negative regulation of protein secretionD(3) dopamine receptorHomo sapiens (human)
musculoskeletal movement, spinal reflex actionD(3) dopamine receptorHomo sapiens (human)
regulation of dopamine uptake involved in synaptic transmissionD(3) dopamine receptorHomo sapiens (human)
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transductionD(3) dopamine receptorHomo sapiens (human)
prepulse inhibitionD(3) dopamine receptorHomo sapiens (human)
positive regulation of dopamine receptor signaling pathwayD(3) dopamine receptorHomo sapiens (human)
negative regulation of adenylate cyclase activityD(3) dopamine receptorHomo sapiens (human)
adenylate cyclase-activating adrenergic receptor signaling pathwayD(3) dopamine receptorHomo sapiens (human)
negative regulation of voltage-gated calcium channel activityD(3) dopamine receptorHomo sapiens (human)
regulation of potassium ion transportD(3) dopamine receptorHomo sapiens (human)
phospholipase C-activating dopamine receptor signaling pathwayD(3) dopamine receptorHomo sapiens (human)
positive regulation of MAPK cascadeD(3) dopamine receptorHomo sapiens (human)
negative regulation of cytosolic calcium ion concentrationD(3) dopamine receptorHomo sapiens (human)
negative regulation of synaptic transmission, glutamatergicD(3) dopamine receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (3)

Processvia Protein(s)Taxonomy
dopamine neurotransmitter receptor activity, coupled via Gi/GoD(3) dopamine receptorHomo sapiens (human)
protein bindingD(3) dopamine receptorHomo sapiens (human)
G protein-coupled receptor activityD(3) dopamine receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (2)

Processvia Protein(s)Taxonomy
plasma membraneD(3) dopamine receptorHomo sapiens (human)
synapseD(3) dopamine receptorHomo sapiens (human)
plasma membraneD(3) dopamine receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (13)

Assay IDTitleYearJournalArticle
AID504812Inverse Agonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID504810Antagonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID231854Compound was evaluated for affinity ratio of dopamine D2 receptor to dopamine D3 receptor; 1:9.62004Journal of medicinal chemistry, Mar-11, Volume: 47, Issue:6
Selective optimization of side activities: another way for drug discovery.
AID65133Displacement of [125I]iodosulpiride from human Dopamine receptor D3 expressed in CHO cells2003Journal of medicinal chemistry, Oct-09, Volume: 46, Issue:21
Molecular modeling of the three-dimensional structure of dopamine 3 (D3) subtype receptor: discovery of novel and potent D3 ligands through a hybrid pharmacophore- and structure-based database searching approach.
AID226581Selectivity ratio of Ki of D2 receptor to that of D3 receptor1998Bioorganic & medicinal chemistry letters, Oct-06, Volume: 8, Issue:19
NGB 2904 and NGB 2849: two highly selective dopamine D3 receptor antagonists.
AID65783Binding affinity against Dopamine receptor D32004Journal of medicinal chemistry, Mar-11, Volume: 47, Issue:6
Selective optimization of side activities: another way for drug discovery.
AID624210Agonists at Human 5-Hydroxytryptamine receptor 5-HT1A1998European journal of pharmacology, Aug-21, Volume: 355, Issue:2-3
Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a [35S]GTPgammaS binding study.
AID1345783Rat D2 receptor (Dopamine receptors)2000Molecular pharmacology, Jan, Volume: 57, Issue:1
Nonconserved residues in the second transmembrane-spanning domain of the D(4) dopamine receptor are molecular determinants of D(4)-selective pharmacology.
AID1347024Rat D4 receptor (Dopamine receptors)2000Molecular pharmacology, Jan, Volume: 57, Issue:1
Nonconserved residues in the second transmembrane-spanning domain of the D(4) dopamine receptor are molecular determinants of D(4)-selective pharmacology.
AID1345615Human 5-HT1A receptor (5-Hydroxytryptamine receptors)1998European journal of pharmacology, Aug-21, Volume: 355, Issue:2-3
Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a [35S]GTPgammaS binding study.
AID1345833Human D3 receptor (Dopamine receptors)1995The Journal of pharmacology and experimental therapeutics, Dec, Volume: 275, Issue:3
Nafadotride, a potent preferential dopamine D3 receptor antagonist, activates locomotion in rodents.
AID1345788Human D2 receptor (Dopamine receptors)1995The Journal of pharmacology and experimental therapeutics, Dec, Volume: 275, Issue:3
Nafadotride, a potent preferential dopamine D3 receptor antagonist, activates locomotion in rodents.
AID1159607Screen for inhibitors of RMI FANCM (MM2) intereaction2016Journal of biomolecular screening, Jul, Volume: 21, Issue:6
A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (52)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's16 (30.77)18.2507
2000's28 (53.85)29.6817
2010's8 (15.38)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 17.88

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index17.88 (24.57)
Research Supply Index4.08 (2.92)
Research Growth Index4.33 (4.65)
Search Engine Demand Index15.26 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (17.88)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews3 (5.17%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other55 (94.83%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]