Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C22H27N3O2 |
| Molecular Weight | 365.4687 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCCCN1CCC[C@H]1CNC(=O)C2=C(OC)C3=CC=CC=C3C(=C2)C#N
InChI
InChIKey=IDZASIQMRGPBCQ-KRWDZBQOSA-N
InChI=1S/C22H27N3O2/c1-3-4-11-25-12-7-8-17(25)15-24-22(26)20-13-16(14-23)18-9-5-6-10-19(18)21(20)27-2/h5-6,9-10,13,17H,3-4,7-8,11-12,15H2,1-2H3,(H,24,26)/t17-/m0/s1
| Molecular Formula | C22H27N3O2 |
| Molecular Weight | 365.4687 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
Nafadotride is a highly potent and competitive dopamine D3 receptor antagonist (D3DR), with efficacy against D2DR and D4DR as well. Nafadotride displayed a high affinity for dopamine
D2 and D3 receptors, but a low affinity for doparnine D1
and D4. At dopamine D2 and D3 receptors, the potency was
concentrated on the l-enantiomer, which was 7 and 20 times,
respectively, more potent than the d-enantiomer. dl-Nafadotride,
l-nafadotride and d-nafadotride were 6, 10 and 2 times,
respectively, more potent at dopamine D3 than at D2 receptors. As compared to haloperidol, a D 2 receptor preferring antipsychotic, the behavioral profile of
nafadotride is characterized by stimulant properties on locomotor activity of rats habituated to their environment occurring at low dosage, i.e. in the range of 1 mg/kg. In contrast, nafadotride exerts typical D 2 receptor blocking responses at much higher dosage: for instance, about 100-fold higher dosages were required to observe extrapyramidal effects like catalepsy.
Originator
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Dopamine D3 receptor knock-out mice display deficits in locomotor sensitization after chronic morphine administration. | 2010-11-26 |
|
| Curcumin modulates dopaminergic receptor, CREB and phospholipase C gene expression in the cerebral cortex and cerebellum of streptozotocin induced diabetic rats. | 2010-05-31 |
|
| Participation of D 1-4 dopamine receptors in the pro-cognitive effects of angiotensin IV and des-Phe 6 angiotensin IV. | 2010-03 |
|
| Dissociable control of impulsivity in rats by dopamine d2/3 receptors in the core and shell subregions of the nucleus accumbens. | 2010-01 |
|
| Dopamine-oxytocin interactions in penile erection. | 2009-12-03 |
|
| Sex differences in nicotine sensitization and conditioned hyperactivity in adolescent rats neonatally treated with quinpirole: role of D2 and D3 receptor subtypes. | 2009-12 |
|
| Acute neurobehavioral effects of toluene: involvement of dopamine and NMDA receptors. | 2009-11-09 |
|
| Effects of pramipexole on the duration of immobility during the forced swim test in normal and ACTH-treated rats. | 2009-07 |
|
| Attenuation of the effects of d-amphetamine on interval timing behavior by central 5-hydroxytryptamine depletion. | 2009-04 |
|
| Dopamine D2/D3 receptor agonist quinpirole impairs spatial reversal learning in rats: investigation of D3 receptor involvement in persistent behavior. | 2009-03 |
|
| Dopaminergic modulation of risk-based decision making. | 2009-02 |
|
| The D2/D3 agonist PD128907 (R-(+)-trans-3,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol) inhibits stimulated pyloric relaxation and spontaneous gastric emptying. | 2009-01 |
|
| Juvenile methylphenidate modulates reward-related behaviors and cerebral blood flow by decreasing cortical D3 receptors. | 2008-06 |
|
| Effect of D(3) dopamine receptors blockade on the cognitive effects of angiotensin IV in rats. | 2008-06 |
|
| Selegilin exerts antidepressant-like effects during the forced swim test in adrenocorticotropic hormone-treated rats. | 2008-04 |
|
| Microinjection of the preferential dopamine receptor D3 agonist 7-hydroxy-N,N-di-n-propylaminotetralin hydrobromide into the hypothalamic medial preoptic area induced ejaculation in anesthetized rats. | 2007-11-09 |
|
| Effect of quinpirole on timing behaviour in the free-operant psychophysical procedure: evidence for the involvement of D2 dopamine receptors. | 2007-08 |
|
| Mediating effect of dopamine D3 receptors on Jak2 and GABAAalpha1 expression in mouse brains induced by cocaine. | 2007-05-20 |
|
| Behavioral and neuropharmacological characterization of nicotine as a conditional stimulus. | 2007-04-30 |
|
| Ejaculation induced by i.c.v. injection of the preferential dopamine D(3) receptor agonist 7-hydroxy-2-(di-N-propylamino)tetralin in anesthetized rats. | 2007-03-16 |
|
| Dopamine receptors oppositely regulate cocaine-induced transcription factor CREB activation. | 2006-06 |
|
| Activation of D2-like receptors induces sympathetic climactic-like responses in male and female anaesthetised rats. | 2006-06 |
|
| Involvement of adenosine A2A and dopamine receptors in the locomotor and sensitizing effects of cocaine. | 2006-03-10 |
|
| Validation of the l-dopa-induced dyskinesia in the 6-OHDA model and evaluation of the effects of selective dopamine receptor agonists and antagonists. | 2005-12-15 |
|
| Dopamine agonist-induced yawning in rats: a dopamine D3 receptor-mediated behavior. | 2005-07 |
|
| Dopamine D3 modulation of locomotor activity and sleep in the nucleus accumbens and in lobules 9 and 10 of the cerebellum in the rat. | 2005-06 |
|
| Biological effects of pramipexole on dopaminergic neuron-associated genes: relevance to neuroprotection. | 2005-03-29 |
|
| Conversion of the modulatory actions of dopamine on spinal reflexes from depression to facilitation in D3 receptor knock-out mice. | 2004-12-15 |
|
| Prenatal ethanol preferentially enhances reactivity of the dopamine D1 but not D2 or D3 receptors in offspring. | 2004-08-17 |
|
| Effects of dopamine D3 receptor antagonists on spontaneous and agonist-reduced motor activity in NMRI mice and Wistar rats: comparative study with nafadotride, U 99194A and SB 277011. | 2004-07 |
|
| Modulation of the discriminative stimulus effects of mu opioid agonists in rats: I. Effects of dopamine D2/3 antagonists. | 2004-02 |
|
| Modulation of the locomotor activating effects of the noncompetitive NMDA receptor antagonist MK801 by dopamine D2/3 receptor agonists in mice. | 2004-02 |
|
| Central effects of nafadotride, a dopamine D3 receptor antagonist, in rats. Comparison with haloperidol and clozapine. | 2004-01-23 |
|
| The dopamine D3 receptor mediates locomotor hyperactivity induced by NMDA receptor blockade. | 2003-08 |
|
| Role of dopamine D3 receptors in controlling the expression of cocaine sensitization in rats. | 2003-07-18 |
|
| Attenuation of levodopa-induced dyskinesia by normalizing dopamine D3 receptor function. | 2003-06 |
|
| Behavioral response profiles following drug challenge with dopamine receptor subtype agonists and antagonists in developing rat. | 2003-05-22 |
|
| The modulatory actions of dopamine D2/3 agonists and antagonists on the locomotor-activating effects of morphine and caffeine in mice. | 2003-05 |
|
| Respective roles of dopamine D2 and D3 receptors in food-seeking behaviour in rats. | 2003-02 |
|
| Dopamine D3 receptor ligands show place conditioning effect but do not influence cocaine-induced place preference. | 2003-01-20 |
|
| Nafadotride administration increases D1 and D1/D2 dopamine receptor mediated behaviors. | 2002-12 |
|
| Blockade of sensitisation-induced facilitation of appetitive conditioning by post-session intra-amygdala nafadotride. | 2002-08-21 |
|
| Isolation rearing-induced facilitation of Pavlovian learning: abolition by postsession intra-amygdala nafadotride. | 2002-08 |
|
| Locomotor hypoactivity and motor disturbances--behavioral effects induced by intracerebellar microinjections of dopaminergic DA-D2/D3 receptor agonists. | 2002-05-07 |
|
| Repeated imipramine treatment enhances the 7-OH-DPAT-induced hyperactivity in rats: the role of dopamine D2 and D3 receptors. | 2002-05-03 |
|
| Acute and chronic effects of methamphetamine on tele-methylhistamine levels in mouse brain: selective involvement of the D(2) and not D(3) receptor. | 2002-02 |
|
| Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a [35S]GTPgammaS binding study. | 1998-08-21 |
|
| Coexpression of dopamine D1 and D3 receptors in islands of Calleja and shell of nucleus accumbens of the rat: opposite and synergistic functional interactions. | 1998-05 |
|
| Opposite effects of dopamine D2 and D3 receptors on learning and memory in the rat. | 1997-10-08 |
|
| Nafadotride, a potent preferential dopamine D3 receptor antagonist, activates locomotion in rodents. | 1995-12 |
Sample Use Guides
Rodents: At low dosage (0.1-1 mg/kg), nafadotride increases spontaneous locomotion of habituated rats and climbing behavior of mice, at doses that do not modify striatal homovanillic acid levels. At high dosage (1-100 mg/kg), nafadotride produces catalepsy and antagonizes apomorphine-induced climbing.
Route of Administration:
Intraperitoneal
In Vitro Use Guide
Curator's Comment: The dopaminergic profile of nafadotride and its enantiomers was determined by in vitro binding studies using membranes from Chinese Hamster
Ovary cells transfected with human dopamine receptor subtype cDNAs.
dl-Nafadotride at concentration of 10 uM was inactive at
various receptors, including adrenergic, adenosine, histamine
and serotonin receptors, but a significant affinity was
initially found for muscariic M1 (Ki value = 1 uM), but not
muscarmnic M2 receptors, serotonin 1A (Ki value = 0.1 uM)
and sigma site (Ki value = 10 nM). In the neuroblastoma x glioma
hybrid cell NG 108-15 transfected with the human dopamine
D3 receptor cDNA, l-nafadotride had no effect when tested
alone at concentrations up to 1 uM. Nafadotride (up to 0.3 uM) has
no effect alone and reversibly antagonized the quinpiroleinduced
increase of mitogenesis in dopamine D2 receptor expressing
cells.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 22:15:05 GMT 2025
by
admin
on
Mon Mar 31 22:15:05 GMT 2025
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| Record UNII |
JP25MZ26IQ
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| Record Status |
Validated (UNII)
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| Record Version |
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JP25MZ26IQ
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390412-29-0
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Nafadotride
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149649-22-9
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