Abstract: Lobeline and nicotine evoke [.sup.3 H]overflow from rat striatal slices preloaded with [.sup.3 H]dopamine ([.sup.3 H]DA). The lobeline-evoked overflow is calcium-independent and not antagonized by mecamylamine, suggesting a mechanism of action other than the stimulation of nicotinic receptors. Whereas nicotine stimulates nicotinic receptors, lobeline inhibits [.sup.3 H]DA uptake into synaptic vesicles and striatal synaptosomes. The results suggest that different mechanisms are responsible for the increase in striatal DA release evoked by lobeline and nicotine. [.sup.3 H]-Dihydrotetrabenazine [.sup.3 H]DTBZ), used routinely to probe a high-affinity binding site-on the vesicular monoamine transporter (VMAT2) binds to vesicle membranes from rat striatum. Lobeline inhibits [.sup.3 H]DTBZ binding with an IC.sub.50 of 0.90 .mu.M, consistent with its IC.sub.50 of 0.88 .mu.M for inhibition of [.sup.3 H]DA uptake into vesicles.

Abstract: Methods are disclosed that suggest the use of lobeline and analogs thereof in treating individuals for drug dependence and withdrawal and for eating disorders.

Abstract: Nicotine analogs that have nicotinic receptor antagonist properties. These compounds have been shown to competitively inhibit dopamine release induced by nicotine. The nicotine analog compounds are useful in the treatment of nicotine abuse, smoking cessation therapy, as an antidote for nicotine intoxication, treatment of cognitive disorders such as Alzheimer's disease and for the treatment of Parkinson's disease.