Savoxepine fails to selectively influence glucose metabolism in the rat limbic system

The [¹⁴C]-2-deoxyglucose method was used to map the in vivo metabolic response of glucose to savoxepine, a novel tetracyclic cyano-dibenzoxepino-azepine. Savoxepine is reported to have higher affinity for dopamine (DA) receptors in the hippocampus than in the striatum and hence should have dose-dependent, anatomically selective actions. Two doses of savoxepine (0.05 mg/kg and 0.5 mg/kg) were compared with haloperidol (1 mg/kg) to test the hypothesis that low doses of savoxepine would display a selective action on limbic brain areas. Results failed to show that low dose savoxepine selectively modifies glucose utilization in the limbic system as previous biochemical studies suggested. In fact, low doses of the drug displayed a potent activity quite similar to haloperidol in effect and localization. The low dose did not produce significantly altered glucose metabolism in the nucleus accumbens or in the lateral habenular nucleus as observed with most other neuroleptics, suggesting a lack of antipsychotic action at this dose. Our findings demonstrate the difficulty of designing a neuroleptic with a preferential blockade of limbic DA receptors and point to the need for functional assessment of regional receptor binding differences.