Pharmacology for Anaesthesia and Intensive Care

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SECTION IV Other important drugs

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Centralnervous system

Hypnotics and anxiolytics


Antidepressants


Anticonvulsants

Hypnotics and anxiolytics

Physiology

γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter within the CNS

and acts via two different receptor subtypes, GABAAand GABAB:


GABAA–this receptor is aligand-gatedCl−ion channel. It consists of five

subunits (2α,β,δandγ–each having a number of variants) arranged to

form a central ion channel. GABA binds to and activates GABAAreceptors and

increases the opening frequency of its Cl− channel, augmenting Cl−

conductance and thereby hyperpolarizing the neuronal membrane. Cl−ion

conductance is potentiated by the binding of BDZs to the α subunit of

the activated receptor complex. GABAA receptors are essentially (but not

exclusively) postsynaptic and are widely distributed throughout the CNS.


GABAB–this receptor ismetabotropic(i.e. acts via a G-protein and second messen-

gers), and when stimulated it increases K+conductance, thereby hyperpolarizing

the neuronal membrane. GABABreceptors are located both presynaptically on

nerve terminals and postsynaptically in many regions of the brain, as well as in the

dorsal horn of the spinal cord. Baclofen acts only via GABABreceptors to reduce

spasticity.

BDZs modulate the effects of GABA at GABAAreceptors. The specificα-subunit type

determines the BDZ pharmacology – anxiolytic or sedative. Two BDZ receptor sub-

types have been identified: BZ 1 ,found in the spinal cord and cerebellum – respon-

sible for anxiolysis; and BZ 2 ,found in the spinal cord, hippocampus and cerebral

cortex – responsible for sedative and anticonvulsant activity.