Use of Lobeline Compounds in the Treatment of Central Nervous System Diseases and Pathologies

Lobeline and nicotine evoke [3H]overflow from rat striatal slices preloaded with [3H]dopamine ([3H]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 [3H]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. [3H]-Dihydrotetrabenazine [3H]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 [3H]DTBZ binding with an IC50 of 0.90 μM, consistent with its IC50 of 0.88 μM for inhibition of [3H]DA uptake into vesicles. These results suggest that the action of lobeline is similar to that of amphetamine and that it specifically interacts with DTBZ sites on VMAT2 to inhibit DA uptake into synaptic vesicles. d-amphetamine inhibits [3H]DTBZ binding to vesicle membranes with an IC50 of 39.4 μM, a concentration 20 times greater than reported for inhibition of VMAT2 function, suggesting that d-amphetamine interacts with a different site than lobeline on VMAT2 to inhibit monoamine uptake. These results suggest the use of lobeline and analogs thereof in treating individuals for diseases and pathologies of the central nervous system

Blockade of alpha 2-adrenergic receptors in prelimbic cortex: impact on cocaine self-administration in adult spontaneously hypertensive rats following adolescent atomoxetine treatment

RATIONALE: Research with the spontaneously hypertensive rat (SHR) model of attention deficit/hyperactivity disorder demonstrated that chronic methylphenidate treatment during adolescence increased cocaine self-administration established during adulthood under a progressive ratio (PR) schedule. Compared to vehicle, chronic atomoxetine treatment during adolescence failed to increase cocaine self-administration under a PR schedule in adult SHR. OBJECTIVES: We determined if enhanced noradrenergic transmission at α2-adrenergic receptors within prefrontal cortex contributes to this neutral effect of adolescent atomoxetine treatment in adult SHR. METHODS: Following treatment from postnatal days 28–55 with atomoxetine (0.3 mg/kg) or vehicle, adult male SHR and control rats from Wistar-Kyoto (WKY) and Wistar (WIS) strains were trained to self-administer 0.3 mg/kg cocaine. Self-administration performance was evaluated under a PR schedule of cocaine delivery following infusion of the α2-adrenergic receptor antagonist idazoxan (0 and 10–56 μg/side) directly into prelimbic cortex. RESULTS: Adult SHR attained higher PR break points and had greater numbers of active lever responses and infusions than WKY and WIS. Idazoxan dose-dependently increased PR break points and active lever responses in SHR following adolescent atomoxetine vs. vehicle treatment. Behavioral changes were negligible after idazoxan pretreatment in SHR following adolescent vehicle or in WKY and WIS following adolescent atomoxetine or vehicle. CONCLUSIONS: α2-Adrenergic receptor blockade in prelimbic cortex of SHR masked the expected neutral effect of adolescent atomoxetine on adult cocaine self-administration behavior. Moreover, greater efficacy of acute idazoxan challenge in adult SHR after adolescent atomoxetine relative to vehicle is consistent with the idea that chronic atomoxetine may downregulate presynaptic α2A-adrenergic autoreceptors in SHR.National Institutes of Health grant DA011716. (DA011716 - National Institutes of Health)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693724/Published versio

Lobeline Compounds as a Treatment for Psychostimulant Abuse and Withdrawal, and for Eating Disorders

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

Nicotinic Receptor Antagonists in the Treatment of Neuropharmacological Disorders

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\u27s disease and for the treatment of Parkinson\u27s disease

Nornicotine Enantiomers for Use as a Treatment for Dopamine Related Conditions and Disease States

Optically active nornicotine compounds as a treatment for dopamine-related conditions and disease states. Such disease states include the treatment of myasthenia gravis, Parkinson\u27s disease, Alzheimer\u27s disease, schizophrenia, eating disorders, ulcers, drug addiction and as a substitute for psycho-stimulant self-administration

Cis-2,6-Disubstituted Piperidines for the Treatment of Psychostimulant Abuse and Withdrawal, Eating Disorders, and Central Nervous System Diseases and Pathologies

Cis-2,6-disubstituted piperdine analogs, or lobeline analogs, having the general formula... To see the remainder of this abstract, please download this patent

Cis-2,6-Disubstituted Piperidines for the Treatment of Psychostimulant Abuse and Withdrawal, Eating Disorders, and Central Nervous System Diseases and Pathologies

Cis-2,6-disubstituted piperdine analogs, or lobeline analogs, having the general formula: To see the remainder of this abstract, please download this patent

Tetrakis-Quaternary Ammonium Salts and Methods for Modulating Neuronal Nicotinic Acteylcholine Receptors

Provided are tetrakis-quaternary ammonium compounds which are modulators of nicotinic acetylcholine receptors. Also provided are methods of using the compounds for modulating the function of a nicotinic acetylcholine receptor, and for the prevention and/or treatment of central nervous system disorders, substance use and/or abuse, and or gastrointestinal tract disorders

1-Methyl-2,6-cis-distyrylpiperidine

The complete molecule of the title compound, C22H25N, is generated by crystallographic mirror symmetry, with two C atoms and the N atom lying on the mirror plane. The central ring adopts a chair conformation and the dihedral angle between the aromatic rings is 56.69 (4)°

Bis-Quaternary Ammonium Salts and Methods for Modulating Neuronal Nicotinic Acetylcholine Receptors

Provided are bis-quaternary ammonium compounds which are modulators of nicotinic acetylcholine receptors. Also provided are methods of using the compounds for modulating the function of a nicotinic acetylcholine receptor, and for the prevention and/or treatment of central nervous system disorders, substance use and/or abuse, and or gastrointestinal tract disorders