Disease relevance of Nafadotride

• At high dosage (1-100 mg/kg), nafadotride, like haloperidol, produces catalepsy and antagonizes apomorphine-induced climbing.(ABSTRACT TRUNCATED AT 250 WORDS)[1]

Psychiatry related information on Nafadotride

• In support of this view low doses of nafadotride, a novel D3 receptor-preferring antagonist, enhances locomotor activity in rodents, a behavioral response opposite to that of current neuroleptics [2].
• The same nafadotride doses potentiated the grooming behavior induced by the D1 dopamine agonist SKF 38393 (10 mg/kg i.p.) as well as the stereotyped response to the D1/D2 agonist apomorphine (0.5 mg/kg s.c.). Stereotyped behavior was also observed in rats concomitantly treated with nafadotride and the D2 agonist quinpirole [3].

High impact information on Nafadotride

• Adult, male, Sprague-Dawley rats were injected subcutaneously (s.c.) with the agonist 7-OH-DPAT (0.1 mg/kg) or antagonist nafadotride (1 mg/kg) at doses previously shown to produce negligible occupancy of D2 receptors in vivo [4].
• Coperfusion with the D3 receptor-preferring antagonist nafadotride dose-dependently blocked the effect of 7-OH-DPAT on nucleus accumbens dopamine efflux [5].
• In D(3) receptor knockout mice, MK-801-induced hyperactivity was weaker than that observed in wild-type mice while BP 897 and nafadotride were inactive [6].
• Nafadotride, UH232 and AJ76, which show a mild preference for D3 versus D2 sites, blocked the PD128,907 DS, and the modestly-selective D3 antagonist, U99194A, was partially effective [7].
• In vivo, all antagonists except GR 103,691 prevented the induction of hypothermia by (+)-PD 128,907 (0.63 mg/kg s.c.) and a further preferential D3 agonist, (+)-7-OH-DPAT (0.16 mg/kg s.c.). On the other hand, haloperidol, (+)-AJ 76, (+)-UH 232 and nafadotride all induced catalepsy in rats, whereas (+)-S 14297, U 99194 and GR 103,691 were inactive [8].

Chemical compound and disease context of Nafadotride

• In mice habituated to the activity cage, nafadotride (0.1-3 mg/kg i.p.) caused a dose-dependent decrease in motor activity but did not affect the hypomotility evoked by either 7-OH-DPAT (0.1 mg/kg) or PD 128907 (0.1 mg/kg) [9].
• In the present study, we compared the effects of dopamine D3 antagonists with different levels of selectivity over D2 receptors (nafadotride, U 99194A and SB 277011) on motor activity as well as on agonist-induced hypoactivity, in mice and rats [9].

Associations of Nafadotride with other chemical compounds

• A comparative in vitro and in vivo pharmacological characterization of the novel dopamine D3 receptor antagonists (+)-S 14297, nafadotride, GR 103,691 and U 99194 [8].
• Haloperidol, (+)-AJ 76, (+)-UH 232, nafadotride and (weakly) U 99194 also enhanced prolactin secretion and striatal dopamine synthesis, whereas (+)-S 14297 and GR 103,691 were inactive [8].
• In contrast the D3 preferring antagonist nafadotride increased cocaine self-administration [10].
• Conversely, D3 receptor antagonists (GR 103691 and nafadotride) increased the MSR in WT but not in D3KO mice [11].

Gene context of Nafadotride

• When administered alone, nafadotride did not change the expression of MOR mRNA [12].

Analytical, diagnostic and therapeutic context of Nafadotride

• Anxiolytic-like effect of nafadotride and PNU 99194A, dopamine D3 receptor antagonists in animal models [13].

References