8/9/2019 Benzodiazepines - Receptor Subunits (Benzodiazepin-Rezeptor-Untereinheiten)

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BENZODIAZEPINE  Z PTO -UNT INH IT N

GABA(A) Receptors and Subunits

The GABA(A) receptor complex has many different subunits, which in turn have isoforms or otherwise

known as subtypes ( (A1-6, B1-4, Y1-3, δ, ε, θ, and P1-2).

Of those subtypes only three of the subunits (Alpha, Beta, Gamma) are B! sensitive"

The A (Alpha) subunit has # subtypes but only a1, a2, a3, and a5 are B! sensitive"

The B (Beta) subunit has $ subtypes, but only b3 subtype is B! sensitive"

The Y (Gamma) subunit has % subtypes, but only y2 subtype is B! sensitive"

&ubunits from only one class (A) or two classes (A and B) can form functional GABA receprots under

experimental conditions, but subunits from three classes (A, B, and Y) are needed for full receptor

function" Threse three subunits also compose most of the GABA(A) receptoris in our brains"

The Alpha (A) subunit

The most important subunit is 'Alpha' and its subtype isoforms (a1,2,3, and 5). The alpha subunit is

responsible for mediatin most of the effects of the ben*os" All ben*os bind to this subunit but they

also all have different affinitie levels to the different subtypes"

A1 subtype: &edation, +espiratory depression, &leep, Ataxia, otor-impairment, Amnesia, Anti-

convulsive, and +einforcin Behavior"

A2 subtype: Anxiolysis, !isinhibition

A3 subtype: Anxiolysis, Anti-.onvulsive, uscle +elaxation

A5 subtype: /earnin and emory, Amnesia, inor &edation

A3 & A5 subtype: &ensorimotor information processin

The Beta (B) and Gamma (Y) subunits

Y2 subtype: 0hysical dependence, respiratory !epression

B3 subtype: Anti-.onvulsive, inor &edation, uscle +elaxation, various other reactions related to

respiration" This subtype is a barbiturate receptor"

8/9/2019 Benzodiazepines - Receptor Subunits (Benzodiazepin-Rezeptor-Untereinheiten)

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Benzs a!!inity t the GABA(A) "e#ept"s

$i%h A1 a!!inity: ida*olam, Tria*olam, 1lunitra*epam, Tema*epam, /ormeta*epam, 2itra*epam,

Broti*olam, 2imeta*epam, /opra*olam, and 1lutopra*epam"

' t de"ate A1 a!!inity: Wide rane !" 1,4 #en$!dia$epine% in&l'din ia$epam, %ta$!lam,

*l'ra$epam, +a$epam, !ra$epam, Alpra$!lam, Br!ma$epam, ama$epam, /'a$epam (hihl0 %ele&tie

a""init0), l!na$epam, eda$epam, !rda$epam, hl!rdia$ep!ide (er0 ea5 a""init0), l!ra$epate, and

most other ben*o as all ben*os are A3 aonists with varyin derees of affinity levels" Also included

here are the 2onben*odia*epine '*-drus' such as !lpidem, alepl!n, !pi&l!ne, and %$!pi&l!ne which

are all hihly selective of the A3 subtype receptor but with only weak to moderate affinity"

$i%h A2 a!!inity: ia$epam, l!na$epam, Br!ma$epam, !ra$epam, Alpra$!lam, ama$epam,

itra$epam, !pra$!lam, !rmeta$epam, and *l't!pra$epam.

oderate A4 affinity5 +a$epam, Pra$epam, Phena$epam, 7ema$epam, *l'nitra$epam, 8ala$epam,

ida$!lam, and other less commonly known ben*os"

ea* A2 a!!inity: Tria*olam, .hlordia*epoxide (stroner affinity for A%), Broti*olam, 6ua*epam,

7etra$epam (%tr!ner a""init0 "!r A3), and a "e !ther%.

$i%h A3 a!!inity: ia$epam, l!na$epam, 7ema$epam, !ra$epam, 7etra$epam, *l'nitra$epam,

imeta$epam, Phena$epam, and Br!ma$epam.

de"ate A3 a!!inity:  Alpra$!lam, Adina$!lam, %ta$!lam, hl!rdia$ep!ide, l!ra$epate, and  

*l'ra$epam.

$i%h Y2 a!!inity (7he%e #en$!% are the m!%t ph0%i&all0 addi&tie)9 7ema$epam, Br!ti$!lam, 7ria$!lam,

 Alpra$!lam, !ra$epam, !pra$!lam, ida$!lam, *l'nitra$epam, l!na$epam, !rmeta$epam,

*l't!pra$epam, itra$epam, imeta$epam, and %ta$!lam

' t mde"ate Y2 affinity5 ia$epam, hl!rdia$ep!ide, +a$epam, and m!%t !ther #en$!%.

$i%h B3 a!!inity: mostly the hypnotics (itra$epam, 7ema$epam, 7ria$!lam, et&)' t mde"ate B3 a!!inity: ia$epam, Alpra$!lam, m!%t !ther #en$!%.