SIGMA-LIGAND S14905 AND LOCOMOTOR-ACTIVITY IN MICE

The binding and locomotor profile of a new sigma ligand, S14905, (isob utyl-N-(1-indan-2yl-piperid-4-yl)N-methyl carbamate, furamate) was stu died. The binding data revealed that S14905 has a high affinity for si gma receptors and very low affinity for both dopamine D-1 and D-2 rece ptors. We have demonstrated that this sigma ligand prevents the locomo tor stimulation induced by morphine (32 and 64 mg/kg), cocaine (16 mg/ kg), amphetamine (4 mg/kg) and adrafinil (32 mg/kg) at doses lower tha n those required to depress spontaneous locomotor activity. The antago nism observed in the present study seems to be more specific of morphi ne induced hyperlocomotion. The high affinity of this compound for sig ma receptors makes it a good choice to study the role of this receptor in the CNS. In addition, S14905 does not directly block dopamine rece ptors but may modulate them in some manner, and would thus warrant fur ther study as a potential atypical antipsychotic agent, and an antagon ist for the hyperactivity induced by opiate drug.