The molecular mechanisms underlying the diverse actions remain unclear, although some of the midazolam mechanism of action and sites of action of benzodiazepines effects are known.
Benzodiazepines appear to produce all their pharmacologic effects by facilitating the actions of gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the CNS.
Benzodiazepines do not activate the GABAA receptors but rather enhance the affinity of the receptors for GABA, as a result of which, there is enhanced opening of chloride gating channels resulting in increased chloride conductance.
This is turn produce hyperpolarization of the postsynaptic cell membrane, while rendering postsynaptic neurons more resistant to excitation, and midazolam mechanism of action .
This resistance to excitation is presumed to be the mechanism by which benzodiazepines produce anxiolysis, sedation, anterograde amnesia, alcohol potentiation and anticonvulsant and skeletal muscle relaxant effects, even seen with midazolam mechanism of action .
Midazolam mechanism of action is due to activation of alpha-1 subunits of GABA-A receptors whereas anxiolytic effect is due to alpha-2 subunit activity. Alpha-1 containing GABAA receptors are the most numerous accounting for 60%.
Alpha-2 subtypes are less common and present in hippocampus and amygdala. GABAA receptors are large macromolecules and provide separate attachment sites for GABA, benzodiazepines, barbiturates, etomidate, propofol, midazolam mechanism of action , neurosteroids and alcohol.
Acting on single receptors by different mechanisms, the benzodiazepines, barbiturates and alcohol can produce synergistic effects to increase GABAA receptor mediated inhibition in the CNS.
This synergy is also the basis of cross tolerance between different classes of drugs. Benzodiazepines decrease adenosine degradation by inhibiting nucleoside transporter.
Adenosine is an important regulator of cardiac function and its physiologic effects convey cardiac protection during myocardial ischaemia.
Midazolam mechanism of action given by intrathecal or epidural injection can produce antinociceptive effect. This could be GABA-mediated, because GABA has been shown to have analgesic properties, though its analgesic property is not as potent as opioids.