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
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 |
|---|---|---|
| Nafadotride, a potent preferential dopamine D3 receptor antagonist, activates locomotion in rodents. | 1995 Dec |
|
| Opposite effects of dopamine D2 and D3 receptors on learning and memory in the rat. | 1997 Oct 8 |
|
| Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a [35S]GTPgammaS binding study. | 1998 Aug 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 May |
|
| Selective inhibition of cocaine-seeking behaviour by a partial dopamine D3 receptor agonist. | 1999 Jul 22 |
|
| Discriminative stimulus properties of the dopamine D3 receptor agonists, PD128,907 and 7-OH-DPAT: a comparative characterization with novel ligands at D3 versus D2 receptors. | 2000 Feb 14 |
|
| Is dopamine implicated in the antidepressant-like effects of selective serotonin reuptake inhibitors in the mouse forced swimming test? | 2001 Dec |
|
| Common discriminative stimulus properties in rats of muscarinic antagonists, clozapine and the D3 preferring antagonist PNU-99194a: an analysis of possible mechanisms. | 2001 Sep |
|
| Locomotor hypoactivity and motor disturbances--behavioral effects induced by intracerebellar microinjections of dopaminergic DA-D2/D3 receptor agonists. | 2001 Sep-Oct |
|
| Isolation rearing-induced facilitation of Pavlovian learning: abolition by postsession intra-amygdala nafadotride. | 2002 Aug |
|
| Blockade of sensitisation-induced facilitation of appetitive conditioning by post-session intra-amygdala nafadotride. | 2002 Aug 21 |
|
| Conversion of the modulatory actions of dopamine on spinal reflexes from depression to facilitation in D3 receptor knock-out mice. | 2004 Dec 15 |
|
| Modulation of the locomotor activating effects of the noncompetitive NMDA receptor antagonist MK801 by dopamine D2/3 receptor agonists in mice. | 2004 Feb |
|
| 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 Jul |
|
| Prenatal ethanol preferentially enhances reactivity of the dopamine D1 but not D2 or D3 receptors in offspring. | 2005 Jan-Feb |
|
| Biological effects of pramipexole on dopaminergic neuron-associated genes: relevance to neuroprotection. | 2005 Mar 29 |
|
| Central effects of nafadotride, a dopamine D3 receptor antagonist, in rats. Comparison with haloperidol and clozapine. | 2005 Mar-Apr |
|
| Behavioral and neuropharmacological characterization of nicotine as a conditional stimulus. | 2007 Apr 30 |
|
| Effect of quinpirole on timing behaviour in the free-operant psychophysical procedure: evidence for the involvement of D2 dopamine receptors. | 2007 Aug |
|
| 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 Mar 16 |
|
| Mediating effect of dopamine D3 receptors on Jak2 and GABAAalpha1 expression in mouse brains induced by cocaine. | 2007 May 20 |
|
| 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 Nov 9 |
|
| Selegilin exerts antidepressant-like effects during the forced swim test in adrenocorticotropic hormone-treated rats. | 2008 Apr |
|
| Juvenile methylphenidate modulates reward-related behaviors and cerebral blood flow by decreasing cortical D3 receptors. | 2008 Jun |
|
| Effect of D(3) dopamine receptors blockade on the cognitive effects of angiotensin IV in rats. | 2008 Jun |
|
| Attenuation of the effects of d-amphetamine on interval timing behavior by central 5-hydroxytryptamine depletion. | 2009 Apr |
|
| Sex differences in nicotine sensitization and conditioned hyperactivity in adolescent rats neonatally treated with quinpirole: role of D2 and D3 receptor subtypes. | 2009 Dec |
|
| Dopamine-oxytocin interactions in penile erection. | 2009 Dec 3 |
|
| Dopaminergic modulation of risk-based decision making. | 2009 Feb |
|
| 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 Jan |
|
| Effects of pramipexole on the duration of immobility during the forced swim test in normal and ACTH-treated rats. | 2009 Jul |
|
| Dopamine D2/D3 receptor agonist quinpirole impairs spatial reversal learning in rats: investigation of D3 receptor involvement in persistent behavior. | 2009 Mar |
|
| Acute neurobehavioral effects of toluene: involvement of dopamine and NMDA receptors. | 2009 Nov 9 |
|
| Dissociable control of impulsivity in rats by dopamine d2/3 receptors in the core and shell subregions of the nucleus accumbens. | 2010 Jan |
|
| Participation of D 1-4 dopamine receptors in the pro-cognitive effects of angiotensin IV and des-Phe 6 angiotensin IV. | 2010 Mar |
|
| Curcumin modulates dopaminergic receptor, CREB and phospholipase C gene expression in the cerebral cortex and cerebellum of streptozotocin induced diabetic rats. | 2010 May 31 |
|
| Dopamine D3 receptor knock-out mice display deficits in locomotor sensitization after chronic morphine administration. | 2010 Nov 26 |
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.
| Name | Type | Language | ||
|---|---|---|---|---|
|
Common Name | English | ||
|
Systematic Name | English |
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
9929059
Created by
admin on Sat Dec 16 08:40:06 GMT 2023 , Edited by admin on Sat Dec 16 08:40:06 GMT 2023
|
PRIMARY | |||
|
64191
Created by
admin on Sat Dec 16 08:40:06 GMT 2023 , Edited by admin on Sat Dec 16 08:40:06 GMT 2023
|
PRIMARY | |||
|
JP25MZ26IQ
Created by
admin on Sat Dec 16 08:40:06 GMT 2023 , Edited by admin on Sat Dec 16 08:40:06 GMT 2023
|
PRIMARY | |||
|
DTXSID1042603
Created by
admin on Sat Dec 16 08:40:06 GMT 2023 , Edited by admin on Sat Dec 16 08:40:06 GMT 2023
|
PRIMARY | |||
|
390412-29-0
Created by
admin on Sat Dec 16 08:40:06 GMT 2023 , Edited by admin on Sat Dec 16 08:40:06 GMT 2023
|
PRIMARY | |||
|
Nafadotride
Created by
admin on Sat Dec 16 08:40:06 GMT 2023 , Edited by admin on Sat Dec 16 08:40:06 GMT 2023
|
PRIMARY | |||
|
149649-22-9
Created by
admin on Sat Dec 16 08:40:06 GMT 2023 , Edited by admin on Sat Dec 16 08:40:06 GMT 2023
|
NON-SPECIFIC STEREOCHEMISTRY |
ACTIVE MOIETY
