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


CONCLUSIONS
CSL enantiomers are D1/D2 mixed antagonists as (-)-SPD. (-)-CSL is the most, while (+)-CSL is the least, potent one among them.
Zhang
X X
XX
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
Jin
G Z
GZ
D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001600:Berberine Alkaloids / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004594:Electrophysiology; D008297:Male; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013378:Substantia Nigra / Q000502:physiology*
C099468:12-chloroscoulerine; D001600:Berberine Alkaloids; D018492:Dopamine Antagonists; D001599:Berberine; C010513:stepholidine; D001058:Apomorphine