18-MC

Iboga alkaloids, also known as coronaridine congeners, have shown promise in the treatment of alcohol and opioid use disorders. The objective of this study was to evaluate the effects of catharanthine and 18-methoxycoronaridine (18-MC) on dopamine (DA) transmission and cholinergic interneurons in the mesolimbic DA system, nicotine-induced locomotor activity, and nicotine-taking behavior. Utilizing ex vivo fast-scan cyclic voltammetry (FSCV) in the nucleus accumbens core of male mice, we found that catharanthine or 18-MC differentially inhibited evoked DA release...

Herein, we fabricated fluorine-containing, polymer-based, flexible neural probes with fluorinated ethylene propylene (FEP) films as the substrates and photo-crosslinkable fluoropolymers as the passivation material. For fabrication, metal-free Au layer formation on the FEP film, the simultaneous photo-adhesion and photo-patterning technique, and the pulsed-laser scanning probe shaping technique were combined, followed by Au electrode surface modification. The resultant probes achieved a charge injection limit equal to 5...

The sedative and anxiolytic-like activity of two coronaridine congeners, (+)-catharanthine and (-)-18-methoxycoronaridine (18-MC), was studied in male and female mice. The underlying molecular mechanism was subsequently determined by fluorescence imaging and radioligand binding experiments. The loss of righting reflex and locomotor activity results showed that both (+)-catharanthine and (-)-18-MC induce sedative effects at doses of 63 and 72 mg/kg in a sex-independent manner. At a lower dose (40 mg/kg), only (-)-18-MC induced anxiolytic-like activity in naïve mice (elevated O-maze test), whereas both congeners were effective in mice under stressful/anxiogenic conditions (light/dark transition test) and in stressed/anxious mice (novelty-suppressed feeding test), where the latter effect lasted for 24 h...

The antidepressant-like activity of (+)-catharanthine and (-)-18-methoxycoronaridine [(-)-18-MC] was studied in male and female mice using forced swim (FST) and tail suspension tests (TST). The underlying molecular mechanism was assessed by electrophysiological, radioligand, and functional experiments. The FST results showed that acute administration (40 mg/kg) of (+)-catharanthine or (-)-18-MC induces similar antidepressant-like activity in male and female mice at 1 h and 24 h, whereas the TST results showed a lower effect for (-)-18-MC at 24 h...

The purpose of this research was to determine expression profiles of metacaspase (MC) genes during ripening and senescence of two apple cultivars with distinct ripening behavior. "Golden Delicious" and "Fuji" harvested at commercial maturity were used as materials. Our data revealed that flesh firmness, respiration rate, ethylene production, metacaspase (MC) activity, superoxide anion (O2 •- ) production rate, relative electrical conductivity (REC), hydrogen peroxide (H2 O2 ), and malondialdehyde (MDA) contents in "Golden Delicious" were higher than in "Fuji" during ripening...

The primary aim of this study was to determine the anti-neuropathic activity of (±)-18-methoxycoronaridine [(±)-18-MC] and (+)-catharanthine in mice by using the oxaliplatin-induced neuropathic pain paradigm and cold plate test. The results showed that both coronaridine congeners induce anti-neuropathic pain activity at a dose of 72 mg/kg (per os), whereas a lower dose (36 mg/kg) of (+)-catharanthine decreased the progress of oxaliplatin-induced neuropathic pain. To determine the underlying molecular mechanism, electrophysiological recordings were performed on α9α10, α3β4, and α4β2 nAChRs as well as voltage-gated calcium (CaV 2...

To determine whether (+)-catharanthine induces sedative- or anxiolytic/anxiogenic-like activity in male mice, proper animal paradigms were used. The results showed that (+)-catharanthine induces sedative-like activity in the 63-72 mg/Kg dose range in a flumazenil-insensitive manner, but neither this effect nor anxiolytic/anxiogenic-like activity was observed at lower doses. To determine the underlying molecular mechanism of the sedative-like activity, electrophysiological and radioligand binding experiments were performed with (+)-catharanthine and (±)-18-methoxycoronaridine [(±)-18-MC] on GABAA (GABAA Rs) and glycine receptors (GlyRs)...

Alcohol use disorder (AUD) is a leading cause of preventable death in the United States, however existing treatments are ineffective and produce aversive side effects such as nausea and fatigue. One potential therapeutic for AUD is the α3β4 nicotinic acetylcholine receptor (nAChR) antagonist 18-methoxycoronaridine (18-MC). Prior work has shown that 18-MC reduces ethanol consumption in rodent models. The present study sought to further examine the therapeutic potential of 18-MC by testing its effects on nonconsummatory behaviors...

Binge alcohol drinking is a health burden in the United States which has an alarming economic impact. Unfortunately, medications available for alcohol abuse have low efficacy or adverse side effects creating a need to evaluate novel therapies. Growing research suggests that 18-Methoxycoronaridine (18-MC), an α3β4 nicotinic acetylcholine receptor (nAChR) antagonist, may be effective at reducing ethanol consumption. However, its effect on binge-like ethanol consumption and other alcohol behaviors have not been examined...

Ibogaine is an indole alkaloid found in the root bark of the Iboga shrub native to west Africa possessing hallucinogenic properties. For centuries it has been used in religious ceremonies and to gain spiritual enlightenment. However, since the early 1960s, its apparent ability to reduce craving for psychoactive substances including alcohol, cocaine, methamphetamine, opiates, and nicotine has led to its use in detoxification treatments. In many instances, clients receive treatment in non-medical settings, with little by way of robust scientific clinical trials...

The West African iboga plant has been used for centuries by the Bwiti and Mbiri tribes to induce hallucinations during religious ceremonies. Ibogaine, the principal alkaloid responsible for iboga's psychedelic properties, was isolated and sold as an antidepressant in France for decades before its adverse effects precipitated its removal from the market. An ibogaine resurgence in the 1960s was driven by U.S. heroin addicts who claimed that ibogaine cured their opiate addictions. Behavioral pharmacologic studies in animal models provided evidence that ibogaine could blunt self-administration of not only opiates but cocaine, amphetamines, and nicotine...

The coordination properties of 2-picolinehydroxamic acid towards cobalt(II) in aqueous solution were determined by a pH-metric method and confirmed by spectroscopic (UV-Vis and ESI-MS) studies. The results show the formation of mononuclear complexes, as well as of metallacrowns (MC). All methods indicate a high tendency of 2-picolinehydroxamic acid to form cobalt(II) metallacrown 12-MC-4. ESI-MS additionally confirms 15-MC-5 and 18-MC-6, stabilized by a sodium ion and methanol. The complexes observed in the speciation model at a pH about 7...

Background: No electroconvulsive therapy (ECT) study on humans or in animal models has so far examined whether differently composed electrical stimuli exert different cardiac electrophysiological effects at constant electrical dose. The subject is important because cardiac electrophysiological changes may provide indirect information about ECT seizure quality as modulated by stimulus composition. Materials and Methods: Adult female Wistar rats ( n = 20/group) received fixed, moderately suprathreshold (18 mC) electrical stimuli...

BACKGROUND: Studies have examined the effects of electroconvulsive therapy (ECT) on human cardiac electrophysiology. However, no study has so far examined whether these effects vary with the magnitude of the electrical dose used to elicit the seizure. Because the benefits and adverse effects of the ECT seizure are dose-dependent, we examined the effects of different electrical doses of electroconvulsive shocks (ECS) on cardiac electrophysiology in an animal model with a view to determine whether cardiac electrophysiology could be a useful proxy to evaluate the quality of the ECT seizure...

As few studies have examined the relationship between the apolipoprotein E (APOE) gene and clinical outcomes after military-related traumatic brain injury (TBI), we aimed to determine whether the ε4 allele of the APOE gene influences neuropsychiatric symptoms in veterans with a history of mild-to-moderate TBI. Participants included 133 veterans (TBI = 79; military controls [MC] = 54) who underwent APOE genotyping and were divided into ε4+ (TBI = 18; MC = 15) and ε4- (TBI = 61; MC = 39) groups...

In contrast to plasma membrane-expressed nicotinic acetylcholine receptors (nAChRs), mitochondrial nAChRs function in an ion-independent manner by triggering intra-mitochondrial kinases that regulate the release of cytochrome c (Cyt c), an important step in cellular apoptosis. The aim of this study is to determine the structural requirements for mitochondrial α3β4* nAChR activation by measuring the modulatory effects of two noncompetitive antagonists of these receptors, (+)-catharanthine and (±)-18-methoxycoronaridine [(±)-18-MC], on Cyt c release from wild-type and α7-/- mice mitochondria...

The inhibitory activity of coronaridine congeners on human (h) α4β2 and α7 nicotinic acetylcholine receptors (AChRs) is determined by Ca2+ influx assays, whereas their effects on neurons in the ventral inferior (VI) aspect of the mouse medial habenula (MHb) are determined by patch-clamp recordings. The Ca2+ influx results clearly establish that coronaridine congeners inhibit hα3β4 AChRs with higher selectivity compared to hα4β2 and hα7 subtypes, and with the following potency sequence, for hα4β2: (±)-18-methoxycoronaridine [(±)-18-MC]>(+)-catharanthine>(±)-18-methylaminocoronaridine [(±)-18-MAC] ∼ (±)-18-hydroxycoronaridine [(±)-18-HC]; and for hα7: (+)-catharanthine>(±)-18-MC>(±)-18-HC>(±)-18-MAC...

Herein, a new family of LnIII [18-metallacrown-6] compounds with the formula [Fe6 O2 Ln(tBu-sao)6 (OH)(MeO)4 (MeOH)(H2 O)]·6MeOH [Ln = DyIII (1), TbIII (2), GdIII (3), and YIII (4), tBu-saoH2 = 3,5-di-tert-butylsalicylaldoxime] was synthesized through one-pot reactions using tBu-saoH2 , Fe(ClO4 )3 ·6H2 O, and Ln(NO3 )3 ·6H2 O. The four compounds are isostructural, and the encapsulation of a Ln ion in the ring cavity of 18-metallacrown-6 (18-MC-6) was exhibited for the first time. The structural analysis shows a ship-like 18-MC-6 core with a beset lanthanide ion connecting six ring oxygen atoms (OMC )...

BACKGROUND: Anastomotic or "stitch hole" bleeding is common during vascular surgery with synthetic material such as Dacron or polytetrafluoroethylene. Hemostatic adjuncts such as fibrin sealant (FS) may reduce blood loss and operating time in such circumstances. We evaluated the safety and the hemostatic effectiveness of a ready-to-use human plasma-derived FS in vascular surgery. METHODS: Patients with mild/moderate suture line bleeding during elective, open, vascular surgery using synthetic grafts or patches were studied...

RATIONALE: The extent to which non-α4β2 versus α4β2* nAChRs contribute to the behavioral effects of varenicline and other nAChR agonists is unclear. OBJECTIVES: The purpose of this study was to characterize the discriminative stimulus effects of varenicline and nicotine using various nAChR agonists and antagonists to elucidate possible non-α4β2 nAChR mechanisms. METHODS: Separate groups of male C57BL/6J mice were trained to discriminate varenicline (3...