| 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 |
MOL RATIO
1 MOL RATIO (average) |
| 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.
CNS Activity
Originator
Approval Year
PubMed
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
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.
