Effects on Ligand-Gated Ion Channels

Inhalants appear to have significant effects on a superfamily of ligand-gated ion channels, including the GABAj receptor, the glycine receptor, the nico- 

There are similarities between the biological actions of inhalants and those of alcohol and barbiturates (Bowen et al. 1996b). For example, acute administration of inhalants affects motor coordination (Moser and Balster 1981) and induces anxiolysis, whereas chronic administration is associated with physical dependence and withdrawal (Bowen et al. 1996a Evans and Balster 1991, 1993). In addition, some inhalant drugs have anticonvulsant properties (Wood et al. 1984). Like other CNS-depressant agents, inhalants have biphasic effects on spontaneous locomotor activity in rodents, with increased activity seen at lower doses and diminished locomotion seen at higher doses (Cause et al. 1985 Kjellstrand et al. 1985). 

To our knowledge no smdies have examined the effects of nitrites on GABA neuro transmission. However, when NO, the major mediator of the peripheral effects of nitrites, was administered within the paraventricular nucleus, it caused an increase in GABA concentrations (Horn et al. 1994). 

The nicotinic acetylcholine (nACh) receptor also displays sensitivity to inhalants (Bale et al. 2002). To varying degrees, toluene appeared to antagonize the function of nACh receptors that comprise different subunits. At concentrations of 50 pM to 10 mM, toluene produced a reversible, concentration-dependent inhibition of acetylcholine-induced current in Xenopus oocytes expressing various nicotinic receptor subtypes, with the ol — 2 d ct3—P2 subunit combinations being more sensitive to inhibition than other receptor 

Similar to alcohol (Lovinger and White 1991) and volatile anesthetics (Machu and Harris 1994), trichoroethane, trichloroethylene, and toluene enhance 5-HT3 receptor function. All three inhalants significantly and reversibly potentiated, in a dose-dependent manner, 5-HT-activated currents, mediated by mouse 5-HT3 receptors expressed in Xenopus oocytes. Another feature common to these drugs is that the acute use of inhalants, as well as alcohol and volatile anesthetics, can produce nausea and vomiting (Meredith et al. 1989). It is believed that 5-HT3 receptors located in the area postrema mediate this action of alcohol and the volatile anesthetics (Aapro 1991). 

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