Stereoselectivity of presynaptic autoreceptors modulating dopamine release

Area of Science:

• Neuropharmacology
• Neurochemistry

Background:

• Dopamine plays a crucial role in neurotransmission within the central nervous system.
• Dopamine receptors are known to exhibit stereoselectivity, meaning different enantiomers of a drug can have varying effects.
• The role of stereochemistry in presynaptic dopamine autoreceptors remains less understood.

Purpose of the Study:

• To investigate the stereoselective effects of sulpiride and butaclamol enantiomers on dopamine release.
• To determine if presynaptic dopamine autoreceptors exhibit stereoselectivity similar to postsynaptic receptors.

Main Methods:

• Utilized rabbit caudate nucleus slices prelabelled with [3H]dopamine.
• Studied the effects of (R)- and (S)-enantiomers of sulpiride and butaclamol on spontaneous and field stimulation-evoked dopamine release.
• Assessed the antagonism of apomorphine-induced inhibition of dopamine release.

Main Results:

• (S)-Sulpiride and (S)-butaclamol significantly enhanced electrically evoked [3H]dopamine release, while their (R)-enantiomers were less potent or inactive.
• (S)-Sulpiride was 10 times more potent than (R)-sulpiride in enhancing dopamine release.
• The facilitatory effects were observed without altering spontaneous dopamine outflow.
• Active enantiomers of sulpiride and butaclamol antagonized apomorphine's inhibitory effect on dopamine release.

Conclusions:

• Presynaptic inhibitory dopamine autoreceptors in the rabbit caudate nucleus are chemically stereoselective.
• This stereoselectivity mirrors that observed in classical postsynaptic dopamine receptors.
• The findings contribute to understanding the nuanced regulation of dopamine release by autoreceptors.