The Solanaceae family comprises numerous species of economic and pharmacological importance, including the toxic deadly nightshade (Atropa belladonna), bittersweet nightshade (Solanum dulcamara), and black nightshade (Solanum nigrum). These plants are native to Europe, North Africa, and Western Asia, and have been used since ancient times in both ritual practices and medicine. A. belladonna contains potent tropane alkaloids (atropine, hyoscyamine, and scopolamine) and is widely utilized in modern pharmacology, although accidental poisonings still occur, often due to confusion with edible plants or the misuse of herbal and homeopathic preparations. In contrast, S. dulcamara contains glycoalkaloids such as solanine, solasodine, and β-solamarine, while S. nigrum contains solanine, solamargine, and solasonine. Both species have a history of traditional use as narcotics, diuretics, and treatments for skin, rheumatic, and respiratory conditions, as well as for pain, inflammation, fever, and other disorders; however, they also pose significant toxicological risks to humans and animals. Although poisonings from these two species are less common than those caused by A. belladonna, they still occur. A review of the literature identified 41 studies reporting poisoning cases associated with these plants, primarily resulting from berry ingestion. Poisoning typically produces anticholinergic syndrome, underscoring the importance of accurate identification and prompt treatment.

The α7 nicotinic acetylcholine receptor (α7 nAChR) is implicated in organophosphate (OP) poisoning, but the scarcity of potent and subtype-selective small-molecule antagonists has hindered the development of related therapeutic strategies. Based on previous structure-activity relationship (SAR) studies, 43 novel piperidine-spirooxadiazole derivatives were designed, synthesized and evaluated using patch-clamp electrophysiology. Two optimized compounds, Y9 and YZ4, exhibited submicromolar inhibition of α7 nAChR and demonstrated high subtype-selectivity for α7 over other nAChR and muscarinic acetylcholine receptor (mAChR) subtypes. They showed robust neuroprotective effects against paraoxon (POX)-induced cytotoxicity in vitro. Notably, YZ4 displayed favorable pharmacokinetic (PK) profiles, including high oral bioavailability and excellent brain penetration. In a POX-intoxicated mouse model, YZ4 significantly improved survival rates, alleviated seizure severity and mitigated multiorgan injury. These findings demonstrate YZ4 as a promising molecular tool for probing α7 nAChR pathophysiology and a potential therapeutic candidate for OP poisoning.

Cyclizine is a first-generation H1 antihistamine widely used for the treatment of nausea and motion sickness. In addition to its antiemetic properties, it has anticholinergic and central nervous system effects that may confer psychoactive potential. Although generally regarded as a low-risk medication, increasing evidence suggests a potential for misuse, particularly among adolescents and individuals with mental health disorders or substance-use vulnerabilities. Published data on cyclizine toxicity are limited, and paediatric reports of intentional overdose remain scarce. We report a case of intentional cyclizine overdose in a 14-year-old girl with underlying mental health disorders, highlighting the clinical presentation, management considerations, including serial electrocardiographic assessment, and safeguarding implications. This case underscores the need for increased clinician awareness of cyclizine misuse and its potential harms in the paediatric population.

A major weakness in the field of neurogastroenterology research has been a lack of technology to determine the spatial and temporal coordination of electrical activity along the gastrointestinal (GI) tract in-vivo, without requiring a surgical procedure. To overcome this weakness, we developed a miniaturized endoscope consisting of 128 iridium oxide recording sensors that allowed us to make high resolution intraluminal electrophysiological recordings in-vivo from the mucosal surface of the terminal large intestine of anesthetized mice. Recordings revealed discharges of smooth muscle action potentials organized into complex spatiotemporal patterns. The patterns were modified by pharmacological agents donepezil and atropine that stimulated or suppressed cholinergic neurotransmission, respectively. The patterns were also ablated by benzalkonium chloride, known to disrupt the function of the enteric nervous system. The endoscope was further validated under ex-vivo recording conditions, where blocking enteric neural activity with tetrodotoxin (TTX) again altered spontaneously occurring action potential patterns. This approach offers a unique opportunity to easily characterize normal and dysfunctional patterns of GI electrical activity in genetically modified and/or diseased mouse models, including drug discovery and high-throughput studies.

In a patient with belladonna poisoning, symptom recurrence was accompanied by a rebound in drug concentration. This suggests reabsorption of residual alkaloids during impaired intestinal peristalsis. The case emphasizes the importance of carefully monitoring bowel motility in the management of belladonna poisoning to prevent delayed or recurrent toxic manifestations.

Resurgence of sarin use in the Syrian conflict demonstrates that chemical weapons are a vivid threat. Like other organophosphate compounds, sarin inhibits acetylcholinesterase resulting in cholinergic crisis. The current antidote therapy includes atropine (a muscarinic cholinergic antagonist) + an oxime (e.g., pralidoxime) to reactivate the inhibited cholinesterases. Long-term sequelae reported in victims of the 1995 Tokyo subway sarin attack emphasize the need to improve neuroprotection and to delineate more precise biomarkers of intoxication severity. Previously, we proposed that brain oscillations could indicate exposure severity to a sublethal dose of a neurotoxic agent. In the present study, we evaluated the effects of atropine + pralidoxime in mice exposed to a sublethal dose of sarin (0.9 LD50) on changes in short-term recovery, brainwaves and behavioral patterns. We demonstrated the benefits of the antidotes on alleviation of the sarin-induced encephalopathy, stabilization of brain oscillations, and attenuation of anhedonia behavior. Nevertheless, mice exhibited work memory impairments associated with the disruption of theta oscillations during the task, the disruption of sleep architecture and the anxiety-like behavior when exposed to the non-convulsive sarin dose. These outcomes were not mitigated by atropine + pralidoxime administration. Our findings suggest that the currently recommended antidote for sarin poisoning provides only partial neuroprotection. Despite stabilizing brain waves in resting state, current antidote is not effective in preventing long-term neurobehavioral complications.

Preclinical evaluation of oximes as antidotes for organophosphorus nerve agent (OPNAs) poisoning is predominantly based on protection ratio of the antidote against lethal doses. Developing protection indexes involves considerable animal distress and, due to the limited precision, requires large animal cohorts. This study aimed to establish an in vivo model for evaluating new therapeutic substances more aligned with the 3R principles that also enables detailed quantification of specific biological effects to better understand the impact of treatment. Anesthetized Sprague-Dawley rats were tracheostomized and connected to a small animal ventilator allowing simultaneous registration of respiratory function. Rats were exposed to 1xLD50 VX or tabun, and progression of poisoning was monitored in real-time through measurements of respiratory resistance (RRS) over a 30-min period. Additional assessments included clinical symptoms and acetylcholine esterase (AChE) inhibition in blood. Pre-treatment with oxime (obidoxime, HI-6, RS194B) or atropine were used to validate the model. Exposure to OPNAs resulted in rapid increases in RRS to 250-300 % above baseline. HI-6 and obidoxime were the most effective treatments, mitigating both respiratory and enzymatic effects of OPNA poisoning, while RS194B treatment delayed onset of symptoms but did not fully reverse toxicity. Tabun-inhibited AChE was generally more resistant to reactivation with oximes than VX- inhibited enzymes. The findings indicate that maintaining AChE activity above 15-20 % is sufficient to restore respiratory function and alleviate symptoms to levels comparable to unexposed controls. This study highlights the value of high-sensitivity, real-time monitoring of physiological metrics like respiratory resistance in evaluating novel antidotes for OPNA poisoning.

Bungarus multicinctus is one of the most venomous and lethal snake species in mainland China, with envenomation resulting in a mortality rate as high as 23%. Currently, antivenin against B. multicinctus remains the gold standard for treating bites from this species. However, in remote mountainous areas or rural regions of China, access to antivenin may be delayed or unavailable following a bite. The lethal components of B. multicinctus venom include α-, β-, γ- and κ-bungarotoxins, which act on either the presynaptic or postsynaptic membrane, thereby altering acetylcholine levels in the synaptic cleft. This study aims to evaluate pharmaceutical agents that confer prophylactic or protective effects against bungarotoxins and neurotoxin-rich snake venoms. Based on theoretical considerations, we postulate that certain anticholinergic or anticholinesterase agents may exhibit potential protective efficacy against these venom components. This study investigated the protective effects of clinically standard anticholinergic and anticholinesterase agents-scopolamine, neostigmine methylsulfate, bethanechol chloride, pilocarpine hydrochloride, and atropine sulfate-against different bungarotoxins and wide distribution neurotoxin-rich crude snake venoms (B. multicinctus, Naja atra and Ophiophagus hannah). Our results showed that neostigmine methylsulfate and atropine sulfate exerted significant protective effects (P < 0.01) against three-finger toxins contained in B. multicinctus venom, including α-bungarotoxin, γ-bungarotoxin, α-bungarotoxin+γ-bungarotoxin combinations, β-bungarotoxin+α-bungarotoxin combinations, and β-bungarotoxin+γ-bungarotoxin combinations. In mice animal models treated with B. multicinctus antivenin, neostigmine methylsulfate and atropine sulfate retained profound protective effects (P < 0.01) against β-bungarotoxin+α-bungarotoxin and β-bungarotoxin+γ-bungarotoxin mixtures. However, these clinic-used drugs showed no significant protective effect against B. multicinctus crude venom, with only modest survival time prolongation without statistical significance observed. Under the same conditions, theses drugs showed no effects on king cobra venoms and significantly prompted the death of the tested animals. Present investigation provides a scientific basis for the treatment of B. multicinctus bites in remote mountainous areas or rural regions of southern China. Upon confirming victims were bitten by B. multicinctus, administering atropine sulfate or neostigmine methylsulfate as emergency treatment might provide supplementary benefits for subsequent care. Importantly, the administration of clinic used drugs does not interfere with the efficacy of B. multicinctus antivenin in later treating stages.

Datura is a poisonous plant, leading to the anticholinergic toxicity of the plant. After attending a marriage celebration, fifty individuals were hospitalized with acute onset of giddiness, blurred vision, excessive sweating, headaches, feeling hot, fearfulness, and dry mouth. Physical examination revealed a flushed appearance, tachycardia, conjunctival congestion, mydriasis, and urinary retention. Anticholinergic poisoning was suspected, and psychiatric consultations revealed that most patients were anxious and fearful with slightly increased psychomotor activity, with 64% exhibiting ataxia, 52% disoriented, and 20% experiencing visual hallucinations. Symptomatic treatment included hydration, short-acting benzodiazepines, and bedside psychiatric counseling, with which all recovered within 2 days. Various psychiatric aspects of diagnosis and management are discussed.

Tropane alkaloids such as atropine and scopolamine are naturally occurring compounds found in various plants of the Solanaceae family, notably Datura species. Although widely used in clinical settings, their potent anticholinergic properties can lead to severe toxic effects. Fatalities involving these substances remain rare, particularly in accidental contexts. Here, the authors report the case of a 58-year-old male who died following the accidental consumption of a meal suspected to have been contaminated with plant material containing tropane alkaloids. At autopsy, blackish vomitus containing unidentified vegetal fragments was observed, and toxicological analyses highlited significant concentrations of both atropine and scopolamine in all postmortem matrices, including femoral and cardiac blood, urine, vitreous humor, and gastric content. No other xenobiotics were detected. This case, consistent with previous toxicological and pathological findings, represents the first documented fatality involving accidental ingestion of tropane alkaloids in a presumed foodborne context. It underscores the potential risks associated with the foraging or handling of toxic plants and underscores the need for greater public health awareness and preventive education.

Organophosphates (OPs) are potent anti-acetylcholinesterase compounds historically used as pesticides and exploited in chemical warfare. Exposure to OPs initiates cholinergic crisis with both peripheral and central effects such as salivation, lacrimation, urination, and defecation (SLUD), and status epilepticus (SE), a prolonged state of seizure. Standard medical countermeasures atropine, oximes, and benzodiazepines reduce mortality, control peripheral symptoms, and terminate SE. However, they do not attenuate the consequences of SE, including neurodegeneration, oxidative stress, neuroinflammation, epilepsy, and associated comorbidities such as cognitive dysfunction. SE induces excessive NADPH oxidase (NOX) synthesis and production of reactive oxygen species, which is a key driver of neurodegeneration and epilepsy. Furthermore, inhibition of NOX in SE-induced epilepsy models reduces neuroinflammation, neurodegeneration, and seizure frequency. Following OP toxicity, treatment with NOX inhibitors diapocynin and mitoapocynin reduced oxidative stress and astrocyte reactivity. This review summarizes the history and development of OPs and the current knowledge on OP toxicity, emphasizing the role of NOX, and the therapeutic potential of NOX inhibitors in treating long-term consequences of acute exposure to OPs.

Standard treatment for Parkinson's disease (PD) is dopamine replacement therapy with L-DOPA. However, chronic treatment often results in abnormal involuntary movements called L-DOPA-induced dyskinesia (LID). Prior evidence indicates that heightened striatal cholinergic tone may contribute to LID. Restoring cholinergic inhibition by targeting the inhibitory M4 muscarinic acetylcholine (ACh) receptor (M4) reduces LID in preclinical models. Although intrinsic striatal sources of ACh have been considered for their role in LID, extrinsic sources of ACh such as the pedunculopontine nucleus (PPN) have not been well investigated for their role in LID. Therefore, the current study employed hemiparkinsonian Long-Evans rats with a PPN-targeted cannula ipsilateral to 6-OHDA lesion. We examined the effect of local unilateral PPN infusion of M4 PAM VU0467154 on LID, motor performance, and c-fos expression within the PPN. It was expected that PPN infusion of VU0467154 would reduce LID, reduce L-DOPA's motor benefit, and globally reduce c-fos expression in the PPN. Contrary to our expectations, PPN infusion of M4 PAM did not significantly affect LID severity. Furthermore, M4 PAM did not alter L-DOPA-mediated motor improvement, and decreased c-fos expression specifically in PPN cholinergic neurons. These results suggest that local PPN ACh dynamics differ from those of the striatum. In the context of prior work, our results suggest that PPN cholinergic modulation or global PPN modulation may be a promising strategy for altering freezing of gait without decreasing motor benefit of L-DOPA and without increasing LID severity.