In vivo binding of SCH 39166: a D-1 selective antagonist

Area of Science:

• Neuropharmacology
• Dopamine Receptor Research

Background:

• SCH 39166 is a previously identified potent and selective D-1 receptor antagonist.
• In vitro studies confirmed SCH 39166's binding to D-1 receptors and its inhibition of rat conditioned avoidance response, a predictor of antipsychotic activity.

Purpose of the Study:

• To investigate the in vivo binding characteristics and selectivity of SCH 39166.
• To assess SCH 39166's interaction with D-1, D-2, and 5-hydroxytryptamine (5-HT)2 receptors in vivo.

Main Methods:

• In vivo receptor binding assays using radiolabeled ligands ([125I]SCH 38840 for D-1, [3H]raclopride for D-2).
• Assessment of receptor protection from N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) inactivation to determine in vivo selectivity.

Main Results:

• SCH 39166 demonstrated potent inhibition of in vivo D-1 receptor binding in rat striatum (ED50 = 0.016 mg/kg s.c.).
• No significant inhibition of D-1 binding in frontal cortex or D-2 binding up to high doses (150 mg/kg s.c.) was observed.
• SCH 39166 significantly protected D-1 receptors from EEDQ inactivation at low doses (0.01 mg/kg s.c.), with weaker protection of 5-HT2 receptors and no protection of D-2 receptors at higher doses.

Conclusions:

• SCH 39166 exhibits high in vivo selectivity for D-1 receptors over D-2 and 5-HT2 receptors.
• The findings support SCH 39166's potential as a selective D-1 antagonist for antipsychotic therapies.