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We have prepared a series of tetrahydro-beta-carbolines (TH beta C), beta-carbolines (beta-C), and other nitrogen heterocycles and evaluated them in vitro with respect to their ability to bind to benzodiazepine receptors. The fully aromatic beta-C's were more potent than their corresponding TH beta C derivatives. When substituents possessing a carbonyl (CO2Me, COCH3, CHO) were introduced at the beta-C 3-position the in vitro potency was augmented. Alcohol substituents (CH2OH, CHOHCH3) demonstrated decreased in vitro potency. The importance of the carbonyl moiety was further demonstrated when beta-carboline-3-carboxylic acid was shown to bind tighter to benzodiazepine receptors at lower pH. A lower pH increases the concentration of the acid and decreases the concentration of the anion. 3-(Hydroxymethyl)-beta-carboline (24), 3-formyl-beta-carboline (25) and 3-acetyl-beta-carboline (27) were benzodiazepine antagonists in vivo. Methyl isoquinoline-3-carboxylate (31a) also had in vitro activity. The same structure-activity relationships seen in beta-C's were also observed for isoquinolines.
M Cain, and
R W Weber, and
F Guzman, and
J M Cook, and
S A Barker, and
K C Rice, and
J N Crawley, and
S M Paul, and
P Skolnick
January 1982,
Progress in clinical and biological research,
M Cain, and
R W Weber, and
F Guzman, and
J M Cook, and
S A Barker, and
K C Rice, and
J N Crawley, and
S M Paul, and
P Skolnick
May 1984,
European journal of pharmacology,
M Cain, and
R W Weber, and
F Guzman, and
J M Cook, and
S A Barker, and
K C Rice, and
J N Crawley, and
S M Paul, and
P Skolnick
July 1981,
Life sciences,
M Cain, and
R W Weber, and
F Guzman, and
J M Cook, and
S A Barker, and
K C Rice, and
J N Crawley, and
S M Paul, and
P Skolnick
January 1983,
Progress in neuro-psychopharmacology & biological psychiatry,
M Cain, and
R W Weber, and
F Guzman, and
J M Cook, and
S A Barker, and
K C Rice, and
J N Crawley, and
S M Paul, and
P Skolnick
January 1994,
Nihon yakurigaku zasshi. Folia pharmacologica Japonica,
M Cain, and
R W Weber, and
F Guzman, and
J M Cook, and
S A Barker, and
K C Rice, and
J N Crawley, and
S M Paul, and
P Skolnick
January 1982,
Progress in clinical and biological research,
M Cain, and
R W Weber, and
F Guzman, and
J M Cook, and
S A Barker, and
K C Rice, and
J N Crawley, and
S M Paul, and
P Skolnick
December 1980,
Medical biology,
M Cain, and
R W Weber, and
F Guzman, and
J M Cook, and
S A Barker, and
K C Rice, and
J N Crawley, and
S M Paul, and
P Skolnick
October 1982,
Acta pharmacologica et toxicologica,
M Cain, and
R W Weber, and
F Guzman, and
J M Cook, and
S A Barker, and
K C Rice, and
J N Crawley, and
S M Paul, and
P Skolnick
January 1979,
Psychopharmacology bulletin,
M Cain, and
R W Weber, and
F Guzman, and
J M Cook, and
S A Barker, and
K C Rice, and
J N Crawley, and
S M Paul, and
P Skolnick
January 1983,
Advances in biochemical psychopharmacology,
