Aminomethyl-2,6-difluorophenols as a novel class of increased lipophilicity GABA(C) receptor antagonists.
3- and 4-(Aminomethyl)-2,6-difuorophenols were tested for activity against the three major classes of GABA receptors. 4-(Amninomethyl)-2,6difluorophenol was shown to be a competitive and somewhat selective antagonist at p1 GABA(C) receptors expressed in Xenopus oocytes (K(B) = 75.5 microM with a 95% Confidence Interval range of 75.2 microM to 75.8 microM). This is the first in a novel class of increased lipophilicity GABA(C) receptor antagonists with little activity at alpha1beta2gamma2 GABA(A) and GABA(B) receptors.
Chebib
M
M
Adrien Albert Laboratory of Medicinal Chemistry, Department of Pharmacology, The University of Sydney, NSW, Australia.
Johnston
G A
GA
Mattsson
J P
JP
Rydström
K
K
Nilsson
K
K
Qiu
J
J
Stevenson
S H
SH
Silverman
R B
RB
D000818:Animals; D001921:Brain / Q000378:metabolism; D018756:GABA Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D009865:Oocytes; D018408:Patch-Clamp Techniques; D010636:Phenols / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D018079:Receptors, GABA / Q000187:drug effects* / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism; D014981:Xenopus
D018756:GABA Antagonists; C087200:GABA-C receptor; D010636:Phenols; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B