3.5.3 Pharmacology I
Lab 8 Determination of the prolongation action of Diazepam on Pentobarbitone induced sleeping time (Cont'd...)
GABA$_A$ receptor has different binding sites for different molecules. It contains total 16 subunits ($\alpha (1-6)$, $\beta (1-3)$, $\gamma (1-3)$, $\delta$, $\varepsilon$, $\pi$, $\theta$). Benzodiazepine I site is located between $\alpha$, and $\gamma$ subunits and benzodiazepine II site either $\alpha 2$, $\alpha 3$, $\alpha 5$ in combination with $\beta$, and $\gamma 2$ subunits.
Benzodiazepines are the second generation of hypnotics, which binds in the benzodiazepine I site. Like barbiturates B GABA$_A$ receptors also induces the GABA mediated inhibition of post synaptic neurons. Different BZDs have different affinities towards the GABA$_A$ receptors. Among all BZDs diazepam has versatile use in neuronal disorders. Diazepam is capable of binding with benzodiazepine I and benzodiazepine II subunits of the receptors and thus diazepam can be used as hypnotics, sedative and anxiolytics (mediated by benzodiazepine I site), anti-epileptics and muscle relaxants (decreasing the muscle tone significantly) Based on the muscle relaxation action of diazepam, it is used to potentate the pentobarbitone induced sleeping time.
Fig. Binding sites in GABA$_A$ receptor
Wister rats (80-120 g)
Normal saline (0.1 ml/g of B. W.), Pentobarbitone (40 mg/kg Body weight), Diazepam (1-4 mg/kg B. w.)
Pan Balance, Marker, Needle (26 G), Syringe, Timer.