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Mechanism of N₂O-induced anxiolysis. N₂O is thought to cause activation of the benzodiazepine (BZ) binding site as its effects are blocked by flumazenil. This action facilitates γ-aminobutyric acid (GABA) activation of its binding site, resulting in chloride ion influx. The increased chloride ion concentration in the neuron might cause activation of calmodulin (CaM), which then activates the enzyme nitric oxide synthase (NOS). NOS converts the amino acid L-arginine (L-Arg) to L-citrulline (L-Cit) and NO, which stimulates the enzyme soluble guanylyl cyclase producing the second messenger cyclic guanosine monophosphate (cyclic GMP). The cyclic GMP, in turn, stimulates a cyclic GMP-dependent protein kinase (PKG) that leads to the anxiolytic drug effect.

Mechanism of N₂O-induced analgesia. N₂O is thought to stimulate the neuronal release of endogenous opioid peptide or dynorphins (DYNs); the molecular aspects of how N₂O initiates this process are as yet unknown. The pre-synaptic nerve terminal takes up L-arginine (L-Arg), which is converted by the enzyme nitric oxide synthase (NOS) to L-citrulline (L-Cit) and nitric oxide (NO). NO appears to be involved in the stimulated release of DYNs. DYNs traverse the synaptic cleft and activate postsynaptic opioid receptors, which belong to the 7-transmembrane–spanning, G protein–coupled superfamily of receptors.

Influence of N₂O on descending inhibitory pathways. N₂O induces release of endogenous opioid peptides (EOP) that activate opioid receptors on γ-aminobutyric acid (GABA)-ergic pontine nuclei. This pathway, in turn, activates descending noradrenergic system in the dorsal horn of the spinal cord that directly inhibits or indirectly inhibits (through a GABA interneuron) nociceptive processing at the level of the primary afferent and second-order neurons that transmit sensory signals up the ascending nociceptive pathway.

Dose-response curve for barbiturates.

Dose-response curve for benzodiazepines.