Neurotransmissions between neurons and via nerves to effector organs and from the peripheral apparatus to afferent fibers are mediated by neurotransmitters. These chemicals are composed of small molecular neurotransmitters including acetylcholine, monoamines such as dopamine, norepinephrine, serotonin, histamine and amino acids (GABA, glycine, glutamate) and large molecular transmitters (peptides such as substance P and neurokinnin). These neurotransmitters are stored in vesicles incorporated within the nerve terminals and are released by exocytosis upon arrival of impulses to the terminals resulting in Ca2+ influx. The neurotransmitters bind to selective receptors and are taken up into the nerve terminals by transporters. Receptors are composed of channel types such as nicotinic, 5-HT3, GABAA, glycine and glutamate receptors and G protein-coupled types. The latter receptors (ex: muscarinic, dopaminergic receptors) with 7-fold transcrossed-amino acids are composed of two second messenger-mediated groups via cAMP and IP3/DG, which activate protein kinase A and C, respectively. Second messengers produce a variety of responses including the iron-channel mechanism in the cell. The structure-activity relationship and receptor specificity is currently an important issue in drug research. One neurotransmitter usually acts on several kinds of receptor subtypes, therefore specific subtype receptor antagonists could be developed as potential candidates of therapeutic drugs.
