Disease relevance of lobeline

• 3. The late hyperventilation and the accompanying sensation of breathlessness occurred in both transplant and control subjects and are therefore likely to be mediated by receptors elsewhere in the body, presumably systemic arterial chemoreceptors stimulated by lobeline [1].
• The lobeline analogs under consideration were investigated as potential nicotinic agonists for the treatment of neurodegenerative disorders, such as Alzheimer's disease [2].
• These effects of lobeline were due partly to the attenuation of METH-induced hyperthermia [3].
• Therefore, lobeline has both temperature-dependent and -independent neuroprotective effects against METH toxicity [3].
• Hypercapnia and stimulation of peripheral chemoreceptors by lobeline excited both early and late units to the same extent, but hypoxic ventilation had a less marked excitatory effect on late fiber activity [4].

Psychiatry related information on lobeline

• Lobeline, an alkaloid from Indian tobacco (Lobelia inflata), is classified as a nicotinic agonist and is currently used as a smoking cessation agent [5].
• Cytisine and lobeline failed to increase locomotor activity at any dose tested [6].
• The deficit in the acquisition of a trace eyeblink classical conditioning was reverted by the systemic administration of carbachol, a nonselective cholinergic muscarinic agonist, but not by lobeline, a nicotinic agonist [7].
• In saline challenge groups, the doses of lobeline examined did not affect spontaneous locomotion nor induced any stereotyped behaviors [8].
• The comparison was made between 6 right handers and 9 left handers (all males) for (i) the dose of lobeline required to produce sensory threshold (viz., first appearance of respiratory sensations) and cough threshold (first appearance of cough); and (ii) latency and duration of sensations for sensory and cough threshold [9].

High impact information on lobeline

• The brainstem and spinal cord were examined in cats administered multiple emetic drugs (cisplatin, lobeline, protoveratrine, naloxone, apomorphine) or control saline injections [10].
• However, some of the nAChR agonists at higher concentrations (1, 1-dimethyl-4-phenylpiperazinium (DMPP) and lobeline), besides their effects on presynaptic nAChRs, are able to inhibit the uptake of NE and 5-HT into nerve terminals, thereby their transmitter releasing effects are extended in time and space [11].
• Generally, all of these analogues had lower affinities at alpha4beta2 and alpha7 nAChRs compared to lobeline, thereby increasing selectivity for VMAT2 [12].
• Lobeline inhibited [3H]DTBZ binding with an IC50 of 0.90 microM, consistent with its previously reported IC50 of 0.88 microM for inhibition of [3H]DA uptake into vesicles [5].
• These results suggest that lobeline specifically interacts with DTBZ sites on VMAT2 to inhibit DA uptake into synaptic vesicles [5].

Chemical compound and disease context of lobeline

• Pretreatment of mice with the microsomal enzyme inducers and inhibitors modified the toxicity of lobeline sulfate [13].
• Less-studied interventions, including hypnosis, acupuncture, aversive therapy, exercise, lobeline, anxiolytics, mecamylamine, opioid agonists, and silver acetate, have assisted some people in smoking cessation, but none of those interventions has strong research evidence of efficacy [14].

Biological context of lobeline

• An increase in [3H]nicotine binding was observed in all regions except cerebellum following chronic infusion with nicotine and anabasine, whereas lobeline did not alter the number or affinity of these binding sites [15].
• Such presumed increased activity in the RARs of man produced by forced expiration to residual volume at the time lobeline-induced sensations were expected did not enhance the sensations in any subject [16].
• 3. Injections of lobeline at doses sufficient to evoke respiratory discomfort lasting 25-32 s (37-73 microgram kg-1) increased the size of the H reflex in soleus with an onset latency of about 10 s and lasting about 20 s [17].
• Lobeline, at the time of maximal effect, dose-dependently produced motor impairment and decreased locomotor activity and body temperature in mice after s.c. treatment [18].
• Lobeline administration (142+/-6 microg/kg) produced either apnea (n=7, latency -2.0+/-0.3 s) or excitation of breathing (n=8, latency -3.5+/-0.3 s) and no change in heart rate [19].

Anatomical context of lobeline

• Interestingly, d-amphetamine inhibited [3H]DTBZ binding to vesicle membranes with an IC50 of 39.4 microM, 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 [5].
• A ganglionic nicotinic antagonist (hexamethonium), but not a skeletal muscle nicotinic antagonist (decamethonium), partially blocked the actions of lobeline [20].
• Furthermore, lobeline did not alter DA or DOPAC levels in the either the nucleus accumbens or striatum [21].
• Lobeline dose dependently inhibited the uptake of [(3)H]NE into rat hippocampal synaptic vesicles and purified synaptosomes with IC(50) values of 1.19 +/- 0.11 and 6.53 +/- 1.37 microM, respectively [22].
• It is proposed that the effect of DMPP and lobeline, to enhance the release of [3H]5-HT from the hippocampus, was mediated by two different mechanisms [23].

Associations of lobeline with other chemical compounds

• However, lobeline does not release dopamine from its presynaptic terminal, but appears to induce the metabolism of dopamine intraneuronally [24].
• The development of lobeline and lobeline analogs with targeted selectivity at VMAT2 represents a novel class of therapeutic agents having good potential as efficacious treatments for methamphetamine abuse [24].
• Inhibitor constants (Ki values) determined in monkey and human liver microsomes were highly correlated (r = 0.97), but two high-affinity inhibitors of the human enzyme (quinidine and lobeline) were approximately 40-fold less potent in monkey livers than in human livers [25].
• RATIONALE: Previous results demonstrated that pretreatment with lobeline attenuates d-methamphetamine self-administration in rats [21].
• The present study evaluated the interaction of lobeline with neuronal nicotinic acetylcholine receptors using two in vitro assays, [(3)H] overflow from [(3)H]dopamine ([(3)H]DA)-preloaded rat striatal slices and (86)Rb(+) efflux from rat thalamic synaptosomes [26].

Gene context of lobeline

• The reaction was sensitive to inhibition by the CYP2D6-selective inhibitors quinidine, quinine, lobeline and norfluoxetine, whereas chemical inhibitors selective for other CYP isoforms failed to affect the reaction [27].
• Lobelane and ketoalkene were 5-fold more potent (Ki = 0.92 and 1.35 microM, respectively) than lobeline (Ki = 5.46 microM) in inhibiting [3H]methoxytetrabenazine binding to VMAT2 in vesicle preparations [28].
• Mesotransdiene and (-)-trans-transdiene competitively inhibited DAT function, whereas lobelane and lobeline acted noncompetitively [28].
• In the present study, lobeline and two structurally simplified analogs were evaluated for activity in muscarinic and nicotinic binding assays, a functional assay for nicotinic receptor activation (86Rb+ efflux from striatal synaptosomes) and an acetylcholinesterase (AChE) assay [29].
• The biosynthesis of lobelia alkaloids. Part III. Intermediates in the biosynthesis of lobeline; biosynthesis of 8, 10-diethyl-lobelidione [30].

Analytical, diagnostic and therapeutic context of lobeline

• Changes in respiratory sensations induced by lobeline after human bilateral lung transplantation [1].
• Chiral separation of lobeline analogs using high performance capillary electrophoresis and derivatized cyclodextrins as chiral additives [2].
• 1. Intravenous injections of lobeline HCl into twenty-six normal young male human volunteers produced sensations of choking, pressure or fumes in the throat and upper chest at a mean threshold dose of 12 micrograms kg-1 [16].
• 5. For transplant subjects studied more than a year after transplantation, there was some evidence that the noxious respiratory sensations evoked by lobeline had returned [1].
• In three out of four cats lobeline had no excitatory effect on the RARs in the absence of normal activity (i.e. when it was injected while artificial respiration was suspended), but on restarting the respiration the activity increased greatly [16].

References