DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Table 17–1
Benzodiazepines: Names and Structures ∗
BENZODIAZEPINE R 1
R 2
R 3
R 7
R 2
′
Alprazolam [Fused triazolo ring] b —H —Cl —H
Brotizolam † [Fused triazolo ring] b —H [Thieno ring A] c —Cl
Chlordiazepoxide a (—) —NHCH 3
—H —Cl —H
Clobazam a,† —CH 3
:O —H —Cl —H
Clonazepam —H :O —H —NO 2
—Cl
Clorazepate —H :O —COO − —Cl —H
Demoxepam a,†,‡ —H :O —H —Cl —H
Diazepam —CH 3
:O —H —Cl —H
Estazolam [Fused triazolo ring] d —H —Cl —H
Flumazenil a [Fused imidazo ring] e —H —F [:O at C 5
] g
Flurazepam —CH 2
CH 2
N(C 2
H 5
) 2
:O —H —Cl —F
Lorazepam —H :O —OH —Cl —Cl
Midazolam [Fused imadazo ring] f —H —Cl —F
Nitrazepam † —H :O —H —NO 2
—H
Nordazepam †,§ —H :O —H —Cl —H
Oxazepam —H :O —OH —Cl —H
CH 2 CH
Prazepam † CH 2 :O —H —Cl —H
CH 2
Quazepam —CH 2
CF 3
:O —H —Cl —F
Temazepam —CH 3
:O —OH —Cl —H
Triazolam [Fused triazolo ring] b —H —Cl —Cl
*
Alphabetical footnotes refer to alterations of the general formula; symbolic footnotes are used for other comments. † Not available for clinical use in
the U.S. ‡ Major metabolite of chlordiazepoxide. § Major metabolite of diazepam and others; also referred to as nordiazepam and desmethyldiazepam.
a
No substituent at position 4, except for chlordiazepoxide and demoxepam, which are N-oxides; R 4
is —CH 3
in flumazenil, in which there is no double
bond between positions 4 and 5; R 4
is :O in clobazam, in which position 4 is C and position 5 is N.
b
H 3 C
C N
N
N
1 C
2
g
No ring C.
c
Br
C
C
S
A
C
C
N
1
5
C
d
HC N
N
N
1 C
2
e
N O
HC
C C OC 2 H
N
5
1 C
2
f
H 3 C
C N
CH
N
1 C
2
effects opposite to those of diazepam in the absence of
benzodiazepine-like agonists and have been termed
inverse agonists; partial inverse agonists also have been
recognized (Chapters 2 and 3). The vast majority of
effects of agonists and inverse agonists can be reversed
or prevented by the benzodiazepine antagonist flumazenil,
which competes with agonists and inverse agonists for
binding to the GABA A
receptor.
Central Nervous System. While benzodiazepines affect
activity at all levels of the neuraxis, some structures are
affected preferentially. The benzodiazepines do not produce
the same degrees of neuronal depression produced