Molecular pharmacology of the glycine receptor chloride channel.

摘要: The glycine receptor (GlyR) Cl(-) channel belongs to the cysteine-loop family of ligand-gated ion receptors. It is best known for mediating inhibitory neurotransmission in motor and sensory reflex circuits spinal cord, although glycinergic synapses are also present brain stem, cerebellum retina. Extrasynaptic GlyRs widely distributed throughout central nervous system they found sperm macrophages. A total 5 GlyR subunits (alpha1-4 beta) have been identified. Embryonic receptors comprise alpha2 homomers whereas adult predominantly alpha beta heteromers a 2:3 stoichiometry. Notably, alpha3 subunit synaptic that mediate onto nociceptive neurons. These specifically inhibited by inflammatory mediators, implying role alpha3-containing pain sensitisation. Because molecules increase current may clinical potential as muscle relaxant peripheral analgesic drugs, this review focuses on molecular pharmacology potentiating substances. Of all substances identified date, we conclude 5HT(3)R antagonists such tropisetron offer most promise therapeutic lead compounds. However, one problem virtually compounds, including analogues, lack specificity GlyR. Another almost nothing about pharmacological properties GlyRs, which subtype choice targeting novel antinociceptive agents. issues need be addressed before GlyR-specific therapeutics can developed.