(-)-stepholidine vs 12-chloroscoulerine enantiomers on firing activity of substantia nigral dopamine neurons.

AIM

To compare the potencies between (-)-stepholidine ((-)-SPD) and 12-chloroscoulerine (CSL) enantiomers on firing of substantia nigra (SN) dopamine (DA) neurons.

METHODS

Extracellular single unit recordings in paralyzed rats.

RESULTS

In rats, (-)-SPD, (-)-, ( +/- )-, and (+)-CSL attenuated i.v. apomorphine (Apo, 10 micrograms.kg-1)-induced inhibition on firing of DA cell, and their ED50 values were 15.1 (11.9-19.4), 7.8 (7.0-8.7), 12.6 (2.0-17.9) micrograms.kg-1, and 2.9 (2.6-3.3) mg.kg-1, respectively. Thus, (-)-CSL was 1 time more potent than (-)-SPD and 371 times more potent than (+)-CSL on D2 receptors. In reserpinized rats, (-)-SPD, (-)-, ( +/- )-, and (+)-CSL blocked the inhibition caused by i.v. 4 mg.kg-1 SKF-38393, with ED50 values of 0.53 (0.51-0.55), 0.51 (0.43-0.60), 1.2 (0.7-2.0), and 5.9 (4.9-7.1) mg.kg-1, respectively. The potency of (-)-CSL was similar to that of (-)-SPD on D1 receptors and 11 times higher than that of (+)-CSL.

CONCLUSION

CSL enantiomers are D1/D2 mixed antagonists as (-)-SPD. (-)-CSL is the most, while (+)-CSL is the least, potent one among them.