Anti-foodborne enteritis effect of galantamine potentially via acetylcholine anti-inflammatory pathway in fish.

Foodborne enteritis has become a limiting factor in aquaculture. Plant protein sources have already caused enteritic inflammation and inhibition in growth performance. Attempts have been made to find an effective solution to foodborne enteritis. Based on the previously suggested fish cholinergic anti-inflammatory pathway, galantamine, a typical cholinesterase inhibitor, was tested for the repression of pro-inflammatory cytokines for soybean meal induced enteritis by injection into grass carp. Both the phylogenetic analysis of cholinesterase, AchR and bioinformatic prediction, indicated galantamine's potential use as an enteritis drug. The result highlighted galantamine's potential effect for anti-enteritis in fish, especially in carps. Subsequently, a 4-week feeding trail using galantamine as an additive, in a zebrafish soybean meal induced enteritis model, demonstrated the prevention of enteritis. The results demonstrated that galantamine could prevent intestinal pathology, both histologically and molecularly, and also maintain growth performance. Reflected by gene expressional analysis, all mechanical, chemical and immune functions of the intestinal barrier could be protected by galantamine supplementation, which aided molecularly in the control of fish foodborne enteritis, through down-regulating Th17 type proinflammatory factors, meanwhile resuming the level of Treg type anti-inflammatory factors. Therefore, the current results shed light on fish intestinal acetylcholine anti-inflammation, by the dietary addition of galantamine, which could give rise to protection from foodborne enteritis.

Feasibility and effects of galantamine on cognition in humans with cannabis use disorder.

BACKGROUND: As long-term use of medicinal and recreational cannabis becomes more common and concentrations of delta-9-tetrahydrocannabinol (THC) in cannabis increase, it is timely to identify strategies to counteract the cognitive effects of cannabinoids. OBJECTIVE: Galantamine is an acetylcholinesterase inhibitor approved for the treatment of Alzheimer's disease and other dementias. This study aimed to investigate the feasibility of galantamine administration to individuals with cannabis use disorder (CUD), and the effects of galantamine on cognition. We hypothesized galantamine would be well tolerated and would not have procognitive effects in the absence of acute cannabis intoxication. METHODS: Thirty individuals with CUD (73.5% male, 26.5% female) participated in a randomized, double-blind, parallel-group trial. Participants completed a baseline session followed by a 10-day outpatient treatment period, during which they received either 8 mg/day of galantamine orally or placebo. Cognitive assessments were conducted at three time points and self-reported measures that may impact cognitive performance (cannabis withdrawal, craving, and mood) were completed at six time points. RESULTS: There were no significant differences in demographic and baseline variables between groups (galantamine vs. placebo). There were no significant adverse effects from galantamine. Cannabis withdrawal and craving continuously decreased over the study. We saw evidence of a modest improvement in cognitive outcomes during the 10-day period, exemplified by a statistically significant increase in measures of response inhibition (increased median reaction time on the Stop Signal Task), and a trend for improvement in measures of attention (increased RVP A'), for both groups. Analyses did not show, however, a significant main effect for treatment or treatment-by-time interactions. CONCLUSIONS: The findings of this pilot study support the feasibility of the administration of galantamine for individuals with CUD. Adequately powered, randomized, placebo-controlled trials are required to investigate the potential of galantamine to improve cognitive deficits associated with CUD.

Development and in vitro evaluation of pressure sensitive adhesive patch for the transdermal delivery of galantamine: Effect of penetration enhancers and crystallization inhibition.

The transdermal route offers an attractive alternative route of drug administration especially for Alzheimer's disease patients through eliminating gastrointestinal side effects and ultimately improving compliance. In this study, we prepared an optimized matrix-type patches for the transdermal delivery of galantamine free base with ex vivo and in vitro evaluation. Four pressure sensitive adhesives with different functional groups, ten penetration enhancers and four drug loadings were tested to determine the optimized patch. The ex vivo permeation of the different formulated patches through human cadaver skin using vertical Franz diffusion cells showed that GELVA GMS 788 was the best pressure sensitive adhesive among the tested polymers. FT-IR and rheological studies done to investigate any potential interactions of the polymer with the drug and/or additives showed the possibility of hydrogen bonding between the drug and pressure sensitive adhesive (PSA), also the additives had a plasticization effect causing increased flexibility of the polymer chains. The optimized formulation had 10%w/w drug loading, 5% w/w limonene as a penetration enhancer, and 5%w/w oleic acid as a crystallization inhibitor. The combination of limonene and oleic acid increased the flux of galantamine by 2.7-fold compared to 1.7-fold when limonene was used alone. The optimized patch exhibited diffusion release kinetics and fitted well to Higuchi's model and yielded a permeation rate of 32.4 ±â€¯1.41 µg/cm2/h across human cadaver skin.

[The application of multichannel electrostimulation and nivalin electrophoresis for the rehabilitative treatment of the patient following plastic surgery in the facial region].

This paper describes for the first time the combined treatment of the patients who underwent plastic surgery for the correction of cosmetic defects in the form of grade II and III senile atrophy of the skin in conjunction with complicated neuropathies of the facial nerve. The essence of the proposed combined treatment consists in using lymphatic drainage massage, medicinal electrophoresis of a nivalin solution, multichannel electrostimulation, and microcurrent therapy with bipolar pulsed currents. The method made it possible to significantly improve the properties of the skin in the facial region, neuro-muscular conductivity, general microcirculation and cerebral circulation in the treated patients.

[The application of electrical stimulation by bipolar pulsed currents and galanthamine electrophoresis for the rehabilitation of patients with diabetes mellitus].

Clinical observations provided evidence of the positive effects of multichannel electrical stimulation by bipolar pulsed currents in combination with galanthamine electrophoresis applied for the treatment of patients with complicated diabetes mellitus. Such treatment facilitated normalization of water and carbohydrate metabolism and reduction of the body weight; moreover, it improved blood circulation and the state of the nervous system.

Effectiveness of donepezil, rivastigmine, and (+/-)huperzine A in counteracting the acute toxicity of organophosphorus nerve agents: comparison with galantamine.

Galantamine, a centrally acting cholinesterase (ChE) inhibitor and a nicotinic allosteric potentiating ligand used to treat Alzheimer's disease, is an effective and safe antidote against poisoning with nerve agents, including soman. Here, the effectiveness of galantamine was compared with that of the centrally active ChE inhibitors donepezil, rivastigmine, and (+/-)huperzine A as a pre- and/or post-treatment to counteract the acute toxicity of soman. In the first set of experiments, male prepubertal guinea pigs were treated intramuscularly with one of the test drugs and 30 min later challenged with 1.5 x LD(50) soman (42 microg/kg s.c.). All animals that were pretreated with galantamine (6-8 mg/kg), 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (+/-)huperzine A survived the soman challenge, provided that they were also post-treated with atropine (10 mg/kg i.m.). However, only galantamine was well tolerated. In subsequent experiments, the effectiveness of specific treatment regimens using 8 mg/kg galantamine, 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (+/-)huperzine A was compared in guinea pigs challenged with soman. In the absence of atropine, only galantamine worked as an effective and safe pretreatment in animals challenged with 1.0 x LD(50) soman. Galantamine was also the only drug to afford significant protection when given to guinea pigs after 1.0 x LD(50) soman. Finally, all test drugs except galantamine reduced the survival of the animals when administered 1 or 3 h after the challenge with 0.6 or 0.7 x LD(50) soman. Thus, galantamine emerges as a superior antidotal therapy against the toxicity of soman.

In vitro galantamine-memantine co-application: mechanism of beneficial action.

Several drugs are in clinical use for symptomatic treatment of Alzheimer's disease patients. Since Alzheimer's disease is known to be associated with down-regulation of the cholinergic and N-methyl-D-aspartate (NMDA) systems, most of these drugs inhibit acetylcholinesterase, potentiate the activity of nicotinic acetylcholine receptors (nAChRs), or modulate NMDA receptors. Galantamine is an anticholinesterase and allosterically potentiates the activity of the nicotinic receptors. We have recently found that galantamine potentiates the activity of NMDA receptors as well. Memantine is unique in that it inhibits the NMDA receptors. We have developed a hypothesis that combining galantamine and memantine will be more effective for improving the patient's conditions than monotherapy with either drug. Patch clamp and intracellular Ca(2+) imaging experiments using rat cortical and hippocampal neurons clearly provided the in vitro bases for our hypothesis. Memantine blocked the extrasynaptic NMDA receptor 100 times more potently than the synaptic NMDA receptor at negative membrane potentials and the block of both types of NMDA receptors was attenuated with depolarization. However, galantamine potentiation of the NMDA receptors was not voltage dependent. Thus, co-application of memantine with galantamine prevented the galantamine potentiation and the activation of extrasynaptic NMDA receptors, but membrane depolarization revealed the galantamine potentiation. Therefore, cell death is expected to be prevented by memantine near the resting potential while the NMDA-mediated synaptic transmission, which is down-regulated in the patients, is maintained and potentiated by galantamine. These results provide in vitro bases for the beneficial actions of galantamine and memantine combinations.

[Current therapy of patients with dementia]. / Aktuelle Antidementiva. Demenzkranken steht eine moderne Therapie zu.

In recent years, the efficacy of symptomatic treatment in patients with Alzheimer's disease has repeatedly been demonstrated in a number of multicenter studies. Such treatment aims both to improve the patient's cognitive abilities and to preserve his or her quality of life and ability to cope with the activities of daily life. In this way the burden on relatives and caregivers is reduced, and the need for home or institutionalized care delayed. Causally effective therapeutic strategies resulting in a cure or the delaying of pathophysiological progression are currently not available, but are being investigated in ongoing clinical and experimental studies. Presently available treatments should be initiated early on, and applied as long as needed, which requires the earliest possible clinical diagnosis by the primary-care physician. The results of initial studies reveal an effect of antidementia agents also in mixed Alzheimer's and vascular dementia, as well as vascular and lewy-body dementia. Efforts to obtain approval for these indications are underway.

[EEG in patients with infantile cerebral palsy before and after the treatment by the method of functional biofeedback]. / EEG bol'nykh detskim tserebral'nym paralichom do i posle lecheniia metodom funktsional'nogo bioupravleniia.

The paper is concerned with a study into the mechanisms of central restructures in formation of a new motor stereotype using functional biomonitoring (FBM) after different pharmacological exposures. There were 117 patients aged 5 to 14 years with spastic forms of infantile cerebral paralysis. Biomonitoring sessions were carried out with the aid of portable indicators. Pharmacological correction was performed by midocalm or galanthamine or by combining the latter one with ganglerone++. The treatment course consisted of 15 training sessions. To study the EEG structure, use was made of the method of computing conditional probabilities of one wave of the EEG, provided it was preceded by any other one. Analysis of the dynamics of the biorhythmical structure of the EEG revealed the common mechanism of restructuring the central components of movements regulation for all the patients' groups using FBM. That mechanism lay in a highly significant increase of interrelated correlations of the main components of the EEG to the alpha-component together with formation or gain of the "alpha-nucleus". The patients' group who underwent biomonitoring sessions after galanthamine and gangleron administration manifested, as compared to the other groups, a highly significant transformation of teta- and delta-components to the alpha-frequency range and enhancement of interrelation of teta-components in the "working" hemisphere. This was coupled with the most beneficial data on the patients' status.

Selective inhibition of human acetylcholinesterase by galanthamine in vitro and in vivo.

We investigated the inhibition of human cholinesterases by galanthamine, an alkaloid of the common snowdrop (galanthus nivalis). In vitro, the compound showed potent enzyme inhibition and 50-fold selectivity for acetylcholinesterase (EC 3.1.1.7) as opposed to butyrylcholinesterase (EC 3.1.1.8). There was no difference between enzyme inhibition by galanthamine in whole blood and separated fractions of plasma and erythrocytes. We conclude that galanthamine does not accumulate in large amounts in red blood cells. In vivo, administration of galanthamine in a healthy volunteer and in a patient who underwent long-term treatment confirmed the selectivity of galanthamine for acetylcholinesterase.