Metal ion interactions with opiates.

Abstract

A number of monovalent and divalent metal ions are known to be vital in the normal functioning of the nervous sytem. However, investigations into the roles of inorganic ions in the actions of narcotic drugs have so far largely involved studies of Ca2+ effects, although experimental evidence has sug­ gested that other ions such as Mg2+, Mn2+, Cu2+, and Na+ may also play a part. Opiate effects have often been associated with Ca2+, which appears to have multiple functions in the nervous system. Thus calcium ions are a component of cell membranes, serving as a membrane stabilizer (1), they are involved in nerve impulse propagation (2, 3), and they alter nerve membrane permeability (4-6). Nerve stimulation causes an influx of ex­ tracellular calcium (7) while calcium ions are also necessary for stimulation­ secretion coupling since neurotransmitter release is a calcium-dependent phenomenon (8-13). Furthermore, calcium ions are involved in postsynap­ tic neurotransmitter effects (14, 15) and in the reuptake of norepinephrine (16, 17). In addition, calcium ions act as important regulators of a number of enzymes such as adenylate cyclase, guanylate cyclase, and phosphodieste­ rase (18-20). Calcium ions are also involved in protein phosphorylation by protein kinase (21, 22) and in the activities of tyrosine and tryptophan hydroxylases (23, 24). The other metal ions that have so far been implicated in narcotic actions have less diverse roles in nervous system function. Changes in the disposi­ tion of sodium (as well as potassium) ions across nerve membranes results