Phaclofen: a peripheral and central baclofen antagonist.

Area of Science:

• Neuropharmacology
• Gastroenterology

Background:

• Baclofen and GABA are neurotransmitters affecting muscle tone and neuronal excitability.
• Specific receptors mediate the actions of baclofen and GABA.
• Phaclofen is a novel phosphonic acid derivative of baclofen.

Purpose of the Study:

• To investigate the antagonistic effects of phaclofen on baclofen and GABA.
• To explore the role of phaclofen in blocking specific neuronal responses.
• To determine the physiological significance of bicuculline-insensitive receptors.

Main Methods:

• Receptor antagonism assays in guinea pig ileum and colon.
• Microelectrophoretic administration in cat spinal cord preparations.
• Electrophysiological recording of neuronal responses.

Main Results:

• Phaclofen reversibly antagonized baclofen and GABA-induced depression of cholinergic responses in guinea pig smooth muscle.
• Phaclofen blocked baclofen's presynaptic inhibition of spinal interneurones but not postsynaptic effects.
• Phaclofen demonstrated selectivity for presynaptic actions.

Conclusions:

• Phaclofen acts as a selective antagonist for certain baclofen and GABA effects.
• Phaclofen can differentiate between presynaptic and postsynaptic receptor actions.
• Phaclofen is a valuable tool for studying bicuculline-insensitive receptors in the central and peripheral nervous systems.