Seminar 11. Sedative-Hypnotic drugs. Anxiolytics. PDF

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Seminar 11. Sedative-Hypnotic drugs. Anxiolytics. Thursday, 23 April 2020Seminar 11.Sedative-Hypnotic drugs.Anxiolytics.I. Sedative-Hypnotic drugs. 2 groups: benzodiazepines and barbiturates Mechanism of action Ligand-gated ion channel Sedative-hypnotic drugs act by interacting with the main inhibit...

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Seminar 11. Sedative-Hypnotic drugs. Anxiolytics. I. Sedative-Hypnotic drugs. • 2 groups: benzodiazepines and barbiturates

Mechanism of action

• Ligand-gated ion channel# • Sedative-hypnotic drugs act by interacting with the main inhibitory pathway (GABA)# !

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• There are 2 types of GABA receptors:# • GABA-A ➝ ligand-gated ion channel, mainly located in CNS# • GABA-B ➝ G-protein coupled receptor, responsible for the function of the skeletal muscles# • GABA-A complex# • Consists of 5 subunits (2α, 1γ and 2β subunits)# • Ligand-binding place ➝ located on α subunit# • The binding of GABA to subunit causes conformational changes ➝ opening central pore ➝ allows chloride ions to enter ➝ entry of chloride ions causes inhibitory signal ➝ suppress further transmission of signals# • 2 types of receptors are located on the surface of the GABA receptor:# 1. Between α and γ subunits ➝ Benzodiazepine receptor# 2. Between α and β subunits ➝ Barbiturates receptor# • Benzodiazepine receptors:# • Are the binding spots for benzodiazepines# • The binding of benzodiazepines stimulate the receptors ➝ causes a more frequent opening of the channel# • Benzodiazepines tend to promote a more frequent opening of the ion channel# • Benzodiazepines do not act if GABA is not bound to binding-site# • Barbiturates receptors:# • Are the binding spots for barbiturates • The binding of barbiturates stimulate the receptors ➝ causes a prolonged state of open channel • Barbiturates do not cause a more frequent opening of the channel ➟ The channel once opened by barbiturates, is going to stay open for a longer period of time • The use of barbiturates is more dangerous ➝ At high doses it can also bind and stimulate the ligand-binding site (= the drug acts as GABA) ➝ this can lead to respiratory depression, coma, cardiovascular depression, or the patient can even die from an overdose1 1

This can’t happen with benzodiazepines, because they can not act without the presence of GABA

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Whalen, K. (z.d.). Figure 9.3 Schematic diagram of benzodiazepine–GABA–chloride ion channel complex. GABA = γ-aminobutyric acid. [figure]. Retrieved from Lippincott Illustrated Reviews Pharmacology p. 122

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