Antagonism of baclofen-induced depression of whole-cell synaptic currents in spinal dorsal horn neurones by the potent GABAB antagonist CGP55845.
The potencies of two GABAB receptor antagonists P-[3-aminopropyl]- P-diethoxymethyl-phosphinic acid (CGP35348) and the novel compound 3-N[1-(S)-(3,4-dichlorophenyl)ethyl]amino-2-(S)-hydroxypropyl-P- benzyl-phosphinic acid (CGP55845) have been compared in an in vitro spinal cord preparation. They have been tested as antagonists of baclofen-induced depression of EPSCs of patch-clamped dorsal horn neurons following electrical stimulation of dorsal roots. Mean EC50 values for the depressant action of baclofen were increased by 50- and 140-fold respectively in the presence of CGP35348 (200 microM) (n = 5) and CGP55845 (100 nM) (n = 4). This potency of CGP55845 is > 1000-fold higher than that reported previously for other GABAB receptor antagonists.
Blake
J F
JF
Department of Pharmacology, School of Medical Sciences, Bristol, U.K.
Cao
C Q
CQ
Headley
P M
PM
Collingridge
G L
GL
Brugger
F
F
Evans
R H
RH
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D001418:Baclofen / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D058788:GABA-B Receptor Antagonists; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010721:Phosphinic Acids / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D010721:Phosphinic Acids; D011412:Propanolamines; C085075:CGP 55845A; C066430:CGP 35348; D001418:Baclofen