Male Sprague–Dawley rats were injected with 12.5 μg 6-hydroxydopamine (6-OHDA) into the right median forebrain bundle to induce a unilateral lesion of the nigrostriatal tract. After 6 weeks, test drugs were administered either alone or in combination with L-DOPA (L-3,4-dihydroxyphenylamine) and the circling behaviour of animals was monitored as an index of anti-Parkinsonian activity.

Intraperitoneal (i.p.) administration of the irreversible MAO-B inhibitor deprenyl (20 mg kg⁻¹) or the imidazoline I₂-site ligands BU224 (14 mg kg⁻¹) and 2-BFI (7 and 14 mg kg⁻¹) produced significant increases in ipsiversive rotations compared to vehicle controls totaling, at the highest respective doses tested, 521±120, 131±37 and 92.5±16.3 net contraversive rotations in 30 (deprenyl) or 60 (BU224 and 2-BFI) min. In contrast, the reversible MAO-A inhibitor moclobemide (2.5–10 mg kg⁻¹) and the reversible MAO-B inhibitor lazabemide (2.5–10 mg kg⁻¹) failed to instigate significant rotational behaviour compared to vehicle.

Coadministration of lazabemide (10 mg kg⁻¹), moclobemide (10 mg kg⁻¹) or 2-BFI (14 mg kg⁻¹) with L-DOPA (20 mg kg⁻¹) significantly increased either the duration or total number of contraversive rotations emitted over the testing period in comparison to L-DOPA alone.

These data suggest that I₂-specific ligands have dual effects in the 6-OHDA-lesioned rat model of Parkinson's disease; a first effect associated with an increase in activity in the intact hemisphere, probably via an increase in striatal dopamine content, and a secondary action which, through the previously documented inhibition of MAO-A and/or MAO-B, increases the availability of dopamine produced by L-DOPA.