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 |
|
| 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 |
|
| Nonconserved residues in the second transmembrane-spanning domain of the D(4) dopamine receptor are molecular determinants of D(4)-selective pharmacology. | 2000 Jan |
|
| Role of dopamine D3 receptors in thermoregulation: a reappraisal. | 2000 Jan 17 |
|
| Identification of the dopamine autoreceptor in the guinea-pig retina as D(2) receptor using novel subtype-selective antagonists. | 2001 Aug |
|
| Is dopamine implicated in the antidepressant-like effects of selective serotonin reuptake inhibitors in the mouse forced swimming test? | 2001 Dec |
|
| Repeated imipramine treatment enhances the 7-OH-DPAT-induced hyperactivity in rats: the role of dopamine D2 and D3 receptors. | 2001 Nov-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 |
|
| Isolation rearing-induced facilitation of Pavlovian learning: abolition by postsession intra-amygdala nafadotride. | 2002 Aug |
|
| 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 Feb |
|
| Respective roles of dopamine D2 and D3 receptors in food-seeking behaviour in rats. | 2003 Feb |
|
| Dopamine D3 receptor ligands show place conditioning effect but do not influence cocaine-induced place preference. | 2003 Jan 20 |
|
| Attenuation of levodopa-induced dyskinesia by normalizing dopamine D3 receptor function. | 2003 Jun |
|
| 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 |
|
| 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 Jun |
|
| Dopamine receptors oppositely regulate cocaine-induced transcription factor CREB activation. | 2006 Jun |
|
| Activation of D2-like receptors induces sympathetic climactic-like responses in male and female anaesthetised rats. | 2006 Jun |
|
| 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 |
|
| 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 |
|
| Effect of D(3) dopamine receptors blockade on the cognitive effects of angiotensin IV in rats. | 2008 Jun |
|
| Dopamine-oxytocin interactions in penile erection. | 2009 Dec 3 |
|
| Effects of pramipexole on the duration of immobility during the forced swim test in normal and ACTH-treated rats. | 2009 Jul |
|
| 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
