Antagonistic effects of isofloxythepin on dopamine D₁ and D₂ receptors and behaviors in rats

1. In vitro, isofloxythepin competed for the binding of [³H]SCH 23390 to striatal D₁ reccptors and for the binding of [³H]spiperone to striatal D₂ receptors with IC₅₀ values of 6.1 (±1.2)x 10^-10 M and 8.4 (±2.6) x 10^-10 M, respectively. Isofloxythepin further inhibited the D₁ receptor mediated, dopamine stimulated adenylate cyclase in the striatal tissue. 2. Fifteen hours after rats were injected with a single dose of isofloxythepin (1 mg/kg, SC), the ex vivo binding curve of [³H]spiperone to striatal D₂ receptors was markedly inhibited, whereas the binding curve of [³H]SCH 23390 to striatal D₁ receptors was unaffected. Fifteen hours after isofloxythepin pretreatment, D₁ agonist SKF 38393 (15 mg/kg, IP)-stimulated grooming behavior was not affected, whereas the D₂ agonist quinpirole (3 mg/kg, IP) stimulated stereotyped behavior was completely abolished. 4. On the basis of the findings from in vivo studies, we conclude that, although isofloxythepin is found to have high affinity for both D₁ and D₂ receptors in vitro, it lacks D₁ antagonistic potency in vivo.