[Circulation time measured by intravenous lobeline: contribution to the study of the mechanism of action of lobeline].
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Administration, Intravenous↗
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Results for “LOBELINE”
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[Determination of lobeline in lobeline grass by the quantitative paper chromatography].
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Chromatography, Paper↗
[The treatment of tobacco smoking by means of lobeline and the effect of lobeline on vegetative and vascular reactions].
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Adult↗
[Stability of injectable lobeline hydrochloride to sterilization with steam and lobeline hydrochloride assay in solutions].
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Drug Stability↗
Lobeline inhibits the neurochemical and behavioral effects of amphetamine.
Lobeline interacts with the dopamine transporter and vesicular monoamine transporter, presynaptic proteins involved in dopamine storage and release. This study used rodent models to assess lobeline-induced inhibition of the neurochemical and behavioral effects of amphetamine. Rat striatal slices were preloaded with [(3)H]dopamine and superfused with lobeline for 30 min, and then with d-amphetamine (0.03-3.00 microM) plus lobeline for 60 min. As predicted, lobeline (1-3 microM) intrinsically increased (3)H overflow but did not inhibit d-amphetamine-evoked (3)H overflow. Consequently, the effect of lobeline on d-amphetamine-evoked endogenous dopamine and dihydroxyphenylacetic acid overflow was assessed. Lobeline (0.1-1 microM) inhibited d-amphetamine (1 microM)-evoked dopamine overflow but did not inhibit electrically evoked (3)H overflow, indicating a selective inhibition of this effect of d-amphetamine. To determine whether the in vitro results translated into in vivo inhibition, the effect of lobeline (0.3-10.0 mg/kg) pretreatment on d-amphetamine (0.1-1.0 mg/kg)-induced hyperactivity in rats and on d-methamphetamine (0.1-3.0 mg/kg)-induced hyperactivity in mice was determined. Doses of lobeline that produced no effect alone attenuated the stimulant-induced hyperactivity. Lobeline also attenuated the discriminative stimulus properties of d-methamphetamine in rats. Acute, intermittent, or continuous in vivo administration of lobeline (1-30 mg/kg) did not deplete striatal dopamine content. Thus, lobeline inhibits amphetamine-induced neurochemical and behavioral effects, and is not toxic to dopamine neurons. These results support the hypothesis that lobeline redistributes dopamine pools within the presynaptic terminal, reducing pools available for amphetamine-induced release. Collectively, the results support a role for lobeline as a potential pharmacotherapy for psychostimulant abuse.
3,4-Dihydroxyphenylacetic Acid↗
Lobeline attenuates locomotor stimulation induced by repeated nicotine administration in rats.
Lobeline inhibits [3H]nicotine binding to rat brain membranes and nicotine-induced [3H]dopamine release from superfused rat striatal slices, indicating that lobeline acts as a nicotinic receptor antagonist. To determine whether lobeline also inhibits the effects of nicotine in vivo, the present study assessed the effect of lobeline pretreatment on nicotine-induced hyperactivity and sensitization. For 12 consecutive days, rats were injected subcutaneously with lobeline (3 mg/kg) or saline, followed 10 min later by nicotine (0.3 mg/kg) or saline injection, and activity was monitored. To determine if lobeline inhibits induction of sensitization to nicotine, 1 or 28 days later, rats were pretreated with saline followed by nicotine or saline. Lobeline attenuated nicotine-induced hyperactivity when both drugs were administered repeatedly. Although an initial injection of lobeline produced hypoactivity, tolerance to this effect developed. Importantly, tolerance did not develop to the lobeline-induced attenuation of nicotine hyperactivity. Lobeline attenuated the induction of sensitization to nicotine 1 day, but not 28 days, after the cessation of lobeline treatment. These results demonstrate that systemic administration of lobeline attenuates the locomotor-activating effects of repeated nicotine injection and the sensitization to nicotine, consistent with lobeline inhibition of nicotinic receptors and/or neurotransmitter transporters.
Animals↗
Respiratory responses of mature horses to intravenous lobeline bolus.
The respiratory stimulant lobeline has been used in equine clinical practice to increase inspiratory and expiratory airflow rates at rest in order to facilitate investigation of both lower and upper airway function. Some of the responses to lobeline in the pony have been reported, but the detailed time course, effect of dose, possible side effects and reproducibility associated with lobeline administration have not been described in the horse. Respiratory airflow rates and oesophageal pressure were measured with a Fleisch No. 5 pneumotachometer and lightweight facemask and a microtip pressure transducer catheter, respectively. The output of the Fleisch pneumotachometer was calibrated for flow rates up to +/- 70 l/s. Seven mature horses with no clinical signs of respiratory disease were studied. Investigations were conducted to determine: (1) the responses to different doses of lobeline (0.15, 0.20, 0.25 and 0.30 mg/kg bwt) as a rapid i.v. bolus (6 horses); (2) arterial blood gases during and after lobeline administration (0.20 mg/kg bwt; 3 horses); and (3) the reproducibility of lobeline-stimulated hyperpnoea (5 horses; 2 doses of 0.20 mg/kg bwt lobeline, 15 min apart). All horses tolerated the lobeline-stimulated hyperpnoea well, although one always coughed or snorted at the onset. Mild tremor was noted following the highest dose in several horses. Apnoea of approximately 40 s was common after the hyperpnoea. Both tidal volume (VT) and frequency (fR) increased with lobeline dose. During peak hyperpnoea at a dose of 0.30 mg/kg bwt, peak inspired flow rate (PIF), peak expired flow rate (PEF) and minute ventilation (VE) were mean +/- s.e. 41+/-5 l/s, 61+/-10 l/s and 920+/-99 l/min, respectively. The hyperpnoea also caused marked changes in arterial PaO2, PaCO2 and pHa at 90 s after lobeline (0.20 mg/kg bwt) administration (mean +/- s.e. 146.0+/-6.9 mmHg, 20.6+/-0.8 mmHg and 7.707+/-0.020, respectively) compared to at rest (mean +/- s.e. 104.0+/-4.0 mmHg, 50.6+/-2.8 mmHg and 7.432+/-0.012). Dynamic lung compliance (Cdyn) was unaltered by lobeline administration. The lobeline-induced hyperpnoea was highly reproducible, with no significant difference in any of the parameters during 2 stimulations 15 min apart. Lobeline induced highly reproducible responses without any apparent adverse effects and may be useful in the investigation of pulmonary function in healthy horses and those with airway disease.
Animals↗
Lobeline augments and inhibits cocaine-induced hyperactivity in rats.
Lobeline has high affinity for nicotinic receptors and alters presynaptic dopamine storage and release in brain. Moreover, lobeline decreases the reinforcing and locomotor-activating properties of methamphetamine, suggesting that lobeline may be a pharmacotherapy for psychostimulant abuse. This study determined if lobeline alters cocaine-induced hyperactivity and if lobeline alters the induction and/or expression of sensitization to cocaine. On Days 1-12, male rats were administered lobeline (0.3 or 1.0 mg/kg) or saline, placed in an automated activity monitor for 20 min, administered cocaine (10, 20 or 30 mg/kg) or saline and returned to the monitor for 60 min. On Day 13, the effect of lobeline on the induction and expression of sensitization to cocaine was determined. Lobeline did not alter the effect of cocaine after acute injection. However, 1.0 mg/kg lobeline attenuated cocaine (10 and 20 mg/kg)-induced hyperactivity after repeated administration and prevented the development of sensitization to these cocaine doses. Interestingly, 0.3 mg/kg lobeline augmented cocaine (10 mg/kg)-induced hyperactivity after repeated administration. Lobeline did not alter the effect of 30 mg/kg cocaine. The present results indicate a complex interaction of lobeline with cocaine and support other research indicating a role for nicotinic receptors in the development of sensitization to psychostimulants.
Animals↗
A novel mechanism of action and potential use for lobeline as a treatment for psychostimulant abuse.
Lobeline, an alkaloidal constituent of Lobelia inflata LINN., has a long history of therapeutic usage ranging from emetic and respiratory stimulant to tobacco smoking cessation agent. Although classified as both an agonist and an antagonist at nicotinic receptors, lobeline has no structural resemblance to nicotine, and structure--function relationships do not suggest a common pharmacophore. Lobeline inhibits nicotine-evoked dopamine release and [3H]nicotine binding, thus acting as a potent antagonist at both alpha3beta2(*) and alpha4beta2(*) neuronal nicotinic receptor subtypes. However, lobeline does not release dopamine from its presynaptic terminal, but appears to induce the metabolism of dopamine intraneuronally. Reevaluation of the mechanism by which lobeline alters dopamine function reveals that its primary mechanism is inhibition of dopamine uptake and promotion of dopamine release from the storage vesicles within the presynaptic terminal, via an interaction with the tetrabenazine-binding site on the vesicular monoamine transporter (VMAT2). Thus, lobeline appears to perturb the fundamental mechanisms of dopamine storage and release. Based on its neurochemical mechanism, the ability of lobeline to functionally antagonize the neurochemical and behavioral effects of the psychostimulants amphetamine and methamphetamine was examined. Lobeline was found to inhibit the amphetamine-induced release of dopamine in vitro, and amphetamine-induced hyperactivity, drug discrimination, and self-administration. However, lobeline does not support self-administration in rats, suggesting a lack of addiction liability. Thus, lobeline may reduce the abuse liability of these psychostimulants. 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.
Amphetamine-Related Disorders↗
Multiple cellular mechanisms mediate the effect of lobeline on the release of norepinephrine.
The complex effect of lobeline on [(3)H]norepinephrine ([(3)H]NE) release was investigated in this study. Lobeline-induced release of [(3)H]NE from the vas deferens was strictly concentration-dependent. In contrast, electrical stimulation-evoked release was characterized by diverse effects of lobeline depending on the concentration used: at lower concentration (10 microM), it increased the release and at high concentration (100 and 300 microM), the evoked release of [(3)H]NE was abolished. The effect of lobeline on the basal release was [Ca(2+)]-independent, insensitive to mecamylamine, a nicotinic acetylcholine receptor antagonist, and to desipramine, a noradrenaline uptake inhibitor. However, lobeline-induced release was temperature-dependent: at low temperature (12 degrees C), at which the membrane carrier proteins are inhibited, lobeline failed to increase the basal release. 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. Lobeline also inhibited Ca(2+) influx induced by KCl depolarization in sympathetic neurons measured with the Fura-2 technique. In addition, phenylephrine, an alpha(1)-adrenoceptor agonist, contracted the smooth muscle of the vas deferens and enhanced stimulation-evoked contraction. Both effects were inhibited by lobeline. Our results can be best explained as a reversal of the monoamine uptake by lobeline that is facilitated by the increased intracellular NE level after lobeline blocks vesicular uptake. At high concentrations, lobeline acts as a nonselective Ca(2+) channel antagonist blocking pre- and postjunctional Ca(2+) channels serving as a counterbalance for the multiple transmitter releasing actions.
Animals↗
Pharmacology of lobeline, a nicotinic receptor ligand.
In this study we investigated the pharmacology of lobeline, a high affinity nicotinic ligand with a unique pharmacological profile, in different in vitro and in vivo tests. Although lobeline displaced [3H]-nicotine binding sites in the rat brain with a Ki of 4.4 nM, it did not activate alpha4beta2 expressed receptors in frog oocytes. The in vivo pharmacological effects of lobeline were highly complex. 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. However, antinociception was present after intrathecal but not after s.c. administration of lobeline in the tail-flick tests. The behavioral effects of lobeline were not blocked by pretreatment with either mecamylamine or dihydro-beta-erythroidine. In addition, lobeline given s.c. enhanced nicotine-induced antinociception in a dose-related manner. No acute tolerance developed to either lobeline's behavioral or antinociceptive effect after s.c. or intrathecal administration, respectively. However, tolerance developed to lobeline's pharmacological effects after chronic treatment with the drug for 10 days (15 mg/kg, s.c. twice a day). Furthermore, cross-tolerance between lobeline and nicotine developed after chronic treatment with either drug. Although the alpha4beta2 receptor is unlikely to mediate the agonist effects of lobeline, our results indicate that lobeline does interact with the nicotinic receptor in a novel fashion.
Animals↗
Influence of lobeline on catecholamine release from the isolated perfused rat adrenal gland.
It has been shown that lobeline (alpha-lobeline) is a lipophilic, nonpyridine, naturally occurring alkaloid obtained from Indian tobacco, Lobelia inflata. The present study was attempted to investigate the effect of lobeline on secretion of catecholamines (CA) evoked by ACh, high K(+), 1.1-dimethyl-4-phenyl piperazinium iodide (DMPP) and (3-(m-chloro-phenyl-carbamoyl-oxy)-2-butynyl trimethyl ammonium chloride (McN-A-343) from the isolated perfused rat adrenal gland and to establish the mechanism of its action. l-Lobeline (30-300 microM) perfused into an adrenal vein for 60 min produced dose- and time-dependent inhibition in CA secretory responses evoked by ACh (5.32 x 10(-3) M), DMPP (10(-4) M for 2 min) and McN-A-343 (10(-4) M for 2 min). However, lower dose of lobeline did not affect CA secretion by high K(+) (5.6 x 10(-2) M), higher dose of it reduced greatly CA secretion of high K(+). l-Lobeline itself did also fail to affect basal catecholamine output. Furthermore, in adrenal glands loaded with lobeline (100 microM), CA secretory response evoked by methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5-carboxylate (Bay-K-8644), an activator of L-type Ca(2+) channels was markedly inhibited while CA secretion by cyclopiazonic acid, an inhibitor of cytoplasmic Ca(2+)-ATPase was not affected. However, nicotine (30 microM), given into the adrenal gland for 60 min, initially rather enhanced CA secretory responses evoked by ACh (5.32 x 10(-3) M) and high K(+) (5.6 x 10(-2) M) followed by great inhibition later, while responses evoked by DMPP (10(-4) M for 2 min) and McN-A-343 (10(-4) M for 2 min) were greatly inhibited. Taken together, these results suggest that lobeline inhibits greatly CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors. Lobeline at lower dose does not affect that by membrane depolarization, but at larger dose inhibits that. It is thought that this inhibitory effect of lobeline may be mediated by blocking the calcium influx into the rat adrenal medullary chromaffin cells without the inhibition of Ca(2+) release from the cytoplasmic calcium store, which is relevant to its nicotinic antagonistic activity. It also seems that there is a difference in the mode of action between nicotine and lobeline in rat adrenomedullary CA secretion.
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
Lobeline inhibits nicotine-evoked [(3)H]dopamine overflow from rat striatal slices and nicotine-evoked (86)Rb(+) efflux from thalamic synaptosomes.
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. To assess agonist interactions, the effect of lobeline was determined and compared to S(-)-nicotine. To assess antagonist interactions, the ability of lobeline to inhibit the effect of S(-)-nicotine was determined. Both S(-)-nicotine (0.1-1 microM) and lobeline (>1.0 microM) evoked [(3)H] overflow from superfused [(3)H]DA-preloaded striatal slices. However, lobeline-evoked [(3)H] overflow is mecamylamine-insensitive, indicating that this response is not mediated by nicotinic receptors. Moreover, at concentrations (<1.0 microM) which did not evoke [(3)H] overflow, lobeline inhibited S(-)-nicotine (0.1-10 microM)-evoked [(3)H] overflow, shifting the S(-)-nicotine concentration-response curve to the right. S(-)-Nicotine (30 nM-300 microM) increased (EC(50) value=0.2 microM) (86)Rb(+) efflux from thalamic synaptosomes. In contrast, lobeline (1 nM-10 microM) did not evoke (86)Rb(+) efflux, and the lack of intrinsic activity indicates that lobeline is not an agonist at this nicotinic receptor subtype. Lobeline completely inhibited (IC(50) value=0.7 microM) (86)Rb(+) efflux evoked by 1 microM S(-)-nicotine, a concentration which maximally stimulated (86)Rb(+) efflux. Thus, the results of these in vitro experiments demonstrate that lobeline inhibits the effects of S(-)-nicotine, and suggest that lobeline acts as a nicotinic receptor antagonist.
Animals↗
Lobeline and structurally simplified analogs exhibit differential agonist activity and sensitivity to antagonist blockade when compared to nicotine.
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. Lobeline displaced [3H]cytisine binding to rat cortical membranes with a mean inhibition constant (KI) value of 16.0 nM, while the lobeline analogs CRM-I-13-1 and CRM-I-32-1 exhibited values of 15.0 and 5.4 microM, respectively. [3H]methylscopolamine was displaced by lobeline with a mean KI value of 37.0 microM while CRM-I-13-1 and CRM-I-32-1 exhibited values of 55.0 and 16.0 microM, respectively. While nicotine stimulated 86Rb+ efflux from striatal synaptosomes in a mecamylamine reversible manner at each concentration tested, lobeline slightly increased 86Rb+ efflux at lower concentrations and reduced efflux at higher concentrations. Further, none of the lobeline effects were reversed with mecamylamine. Although less potent, the two lobeline analogs exhibited a similar pattern of activity. These data may suggest that lobeline and structurally similar compounds bind with different subtype selectivity than nicotine, or exert their agonists effects through non-nicotinic mechanisms. All of the compounds tested were at least several hundred times less potent than physostigmine as AChE inhibitors. While some differences were apparent between the lobeline analog which contained the 2-keto-ethyl portion of lobeline and the analog which contained the phenyl 2-hydroxy-ethyl moiety, each compound was much less active than lobeline in most parameters assessed.
Acetylcholinesterase↗
Lobeline does not serve as a reinforcer in rats.
RATIONALE: Previous results demonstrated that pretreatment with lobeline attenuates d-methamphetamine self-administration in rats. OBJECTIVE: The present experiments determined if lobeline serves as a reinforcer, if it decreases d-methamphetamine-induced reinstatement of d-methamphetamine self-administration, and if it activates the mesolimbic and nigrostriatal dopamine (DA) pathways in Sprague-Dawley male rats. METHODS: The ability of intravenous (IV) lobeline (0.015-0.15 mg/kg per infusion) to engender responding and the ability of lobeline (0.015 and 0.05 mg/kg per infusion) to substitute for d-methamphetamine was determined using the self-administration paradigm. Experiments were also performed to determine if lobeline (1.0 and 3.0 mg/kg) reinstates responding for d-methamphetamine or alters the ability of d-methamphetamine (1.0 mg/kg per infusion) to reinstate responding following extinction. The effect of lobeline (3.0 mg/kg) or d-methamphetamine (1.0 and 3.0 mg/kg) on DA and dihydroxyphenylacetic acid (DOPAC) levels in the nucleus accumbens and striatum were also determined. RESULTS: Lobeline was not self-administered and did not substitute for d-methamphetamine. Also, lobeline did not reinstate responding for d-methamphetamine following extinction nor did it alter d-methamphetamine-induced reinstatement. Furthermore, lobeline did not alter DA or DOPAC levels in the either the nucleus accumbens or striatum. CONCLUSIONS: Taken together, the present results indicate that lobeline decreases d-methamphetamine self-administration by decreasing reward, not by acting as a substitute reinforcer.
3,4-Dihydroxyphenylacetic Acid↗
Effects of lobeline, a nicotinic receptor agonist, on learning and memory.
The effects of (-)-lobeline were assessed in two learning and memory tasks in which nicotine-induced enhancement of performance has previously been demonstrated. Lobeline (19 mumol/kg, IP) administered immediately after inhibitory (passive) avoidance training improved retention performance assessed 24 h later, as rats that received this dose of lobeline took significantly longer to enter the shock compartment on the test day than rats that had been treated with vehicle. Pretraining lobeline treatment (1.9 mumol/kg, IP) significantly improved performance of rats with septal lesions in a spatial discrimination water maze, a finding confirmed when rats were retrained using new spatial locations and vehicle and lobeline treatments were reversed in a crossover design. The effective dose of lobeline in the inhibitory avoidance task was about 10-fold higher than that generally reported for nicotine, and direct comparison of the suppression of locomotor activity shortly after administration of nicotine or lobeline also revealed a 10-fold greater potency for nicotine. In contrast, no difference was found between the effective dose of lobeline in the current study and that we previously found with nicotine in the water maze. These findings suggest that lobeline's effects on the performance of learning and memory tasks may be similar to those of nicotine. Coupled with previous reports that lobeline does not produce the nicotine cue in drug discrimination experiments, this study also suggests that nicotinic receptors involved in the modulation of memory processes may be distinct from those involved in producing the nicotine cue.
Animals↗
Striatal application of nicotine, but not of lobeline, attenuates dopamine release in freely moving rats.
We investigated the physiological role of native low- and high-affinity nicotinic acetylcholine receptors (nAChRs) in regulating dopamine (DA) release from striatal DA terminals. To evaluate the functional interactions of the two receptor subtypes, nicotine (which interacts with both high- and low-affinity nAChRs) and lobeline (which selectively interacts with high-affinity nAChRs) were perfused through a microdialysis probe implanted into the striatum of freely moving rats. The DA content of successive dialysates was quantified by HPLC with an electrochemical detector. A short-lasting (1-min) perfusion of nicotine or lobeline dose-dependently increased the DA content of striatal dialysates. A second application of the same dose of nicotine resulted in an attenuated DA increase, compared with the increase elicited by the first application; however, the DA increase elicited by a second application of lobeline was similar to that of the first lobeline application. The nicotine-induced response was not attenuated when it followed a lobeline perfusion; in contrast, if the nicotine perfusion preceded that of lobeline, the lobeline-induced response was attenuated. In the presence of mecamylamine (a noncompetitive nAChR antagonist), the increase in DA content of striatal dialysate samples induced by either nicotine or lobeline was attenuated. However, in the presence of methyllycaconitine (a preferential antagonist for low-affinity alpha7 homomeric nAChRs), the nicotine response was attenuated but that of lobeline was unaffected. These results suggest that the functional inactivation of striatal nAChRs requires the simultaneous activation of both low- and high-affinity nAChRs. Since lobeline is devoid of reinforcing properties, one might infer that the reinforcing properties of nicotine require the simultaneous activation of high- and low-affinity brain nAChRs.
Aconitine↗
Lobeline attenuates methamphetamine-induced changes in vesicular monoamine transporter 2 immunoreactivity and monoamine depletions in the striatum.
L-Lobeline is an alkaloid that inhibits the behavioral effects of methamphetamine (METH) in rats. No studies have examined the effects of lobeline on the acute and long-term neurochemical changes produced by neurotoxic doses of METH. The effects of lobeline on METH-induced dopamine release, alterations in vesicular monoamine transporter 2 (VMAT-2) distribution, and long-term depletions of dopamine and serotonin (5-HT) content in the rat striatum were examined. METH increased body temperature and dopamine release, decreased VMAT-2 immunoreactivity at 1 and 24 h after METH, and decreased dopamine and 5-hydroxytryptamine (5-HT) content in striatum when examined 7 days later. Prevention of METH-induced hyperthermia attenuated the decrease in VMAT-2 as well as dopamine and 5-HT content. Lobeline pretreatment did not affect METH-induced dopamine release but attenuated the decreases in VMAT-2 after METH and the long-term decreases in striatal dopamine and 5-HT content. These effects of lobeline were due partly to the attenuation of METH-induced hyperthermia. The maintenance of hyperthermia during lobeline + METH exposure restored the effects of METH on decreases in VMAT-2 as well as dopamine and 5-HT content. To examine the effects of lobeline independent of its effects on METH-induced hyperthermia, lobeline was administered after METH when body temperature returned to normal. Lobeline treatment at 5 and 7 h after METH attenuated the METH-induced decreases in synaptosomal, membrane-associated, and vesicular VMAT-2 24 h after METH, as well as the METH-induced decreases in dopamine and 5-HT content 7 days later. Therefore, lobeline has both temperature-dependent and -independent neuroprotective effects against METH toxicity.
Adrenergic Agents↗