The CGP7930 analogue 2,6-di-tert-butyl-4-(3-hydroxy-2-spiropentylpropyl)-phenol (BSPP) potentiates baclofen action at GABA(B) autoreceptors.
The pharmacological actions of 2,6-di-tert-butyl-4-(3-hydroxy-2-spiropentylpropyl)-phenol (BSPP), a putative presynaptic GABA(B) receptor modulator, were examined in electrically stimulated rat neocortical brain slices preloaded with [3H]-GABA or [3H]-glutamic acid. At 10 mmol/L, BSPP inhibited the release of [3H]-GABA in the presence of baclofen, but not that of [3H]-glutamic acid. This effect was sensitive to the GABA(B) receptor antagonist (+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid (Sch 50911). Alone, BSPP had no effect on the release of [3H]-GABA or [3H]-glutamic acid. It is concluded that BSPP selectively potentiates the action of baclofen at GABA(B) autoreceptors, but not heteroreceptors and may be a useful ligand to discriminate between presynaptic GABA(B) receptor subtypes.
Parker
David A S
DA
School of Dentistry, The University of Adelaide, Australia.
Marino
Victor
V
Ong
Jennifer
J
Puspawati
Ni Made
NM
Prager
Rolf H
RH
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D058788:GABA-B Receptor Antagonists; D018698:Glutamic Acid / Q000493:pharmacokinetics; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D019579:Neocortex / Q000187:drug effects* / Q000378:metabolism; D009924:Organ Culture Techniques; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000378:metabolism; D013141:Spiro Compounds / Q000494:pharmacology*; D014316:Tritium / Q000493:pharmacokinetics; D005680:gamma-Aminobutyric Acid / Q000493:pharmacokinetics
C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; C438607:2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl)phenol; C534335:2,6-di-tert-butyl-4-(3-hydroxy-2-spiropentylpropyl)phenol; D058788:GABA-B Receptor Antagonists; D009025:Morpholines; D010636:Phenols; D018080:Receptors, GABA-B; D013141:Spiro Compounds; D014316:Tritium; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D001418:Baclofen