Table 2 Mechanism of action of the 8 newly approved antiepileptic drugs (AEDs) <table><thead><tr><th>AED</th><th>Mechanism of action</th></tr></thead><tbody><tr><td>Clobazam</td><td>Binding to benzodiazepine at the GABA_A ligand-gated chloride channel complex</td></tr><tr><td>Eslicarbazepine</td><td>Use-dependent blockage of voltage-sensitive sodium channels</td></tr><tr><td>Ezogabine</td><td>Positive allosteric modulator of KCNQ2-5; positive allosteric modulator of GABA_A receptors</td></tr><tr><td>Lacosamide</td><td>Slow inactivation of voltage-gated sodium channels; binds to CRMP-2</td></tr><tr><td>Perampanel</td><td>AMPA receptor antagonist</td></tr><tr><td>Pregabalin</td><td>Binding to the α2-δ protein subunit of voltage-gated calcium channels</td></tr><tr><td>Rufinamide</td><td>Use-dependent blockage of voltage-sensitive sodium channels</td></tr><tr><td>Vigabatrin</td><td>Inactivation of GABA transaminase</td></tr></tbody></table>

This pathophysiology diagram illustrates the neurobiological mechanism of benzodiazepine addiction through disinhibition of dopaminergic neurons in the mesolimbic reward system. The illustration is divided into two comparative panels. Panel A (No benzodiazepines) shows a baseline state in the Ventral Tegmental Area (VTA), where a blue GABAergic interneuron releases GABA molecules to inhibit a yellow dopaminergic (DAergic) neuron via GABAA receptors, resulting in 'Low activity' and minimal dopamine release in the Nucleus Accumbens (NAc). A GLUergic neuron is also shown nearby. Panel B (Benzodiazepines bound) depicts the introduction of red benzodiazepine molecules, which bind to GABAA receptors on the GABAergic interneuron. This binding induces 'Disinhibition' of the downstream DAergic neuron (indicated by an 'X' over the inhibitory synapse). Consequently, the DAergic neuron exhibits 'Increased activity,' leading to a significant rise in dopamine release (red molecules) within the NAc. The diagram highlights how benzodiazepines modulate neuronal signaling to trigger the brain's reward circuitry.

This pathophysiology diagram illustrates the mechanism of GABA receptor-mediated inhibition in neurons and the modulatory effects of anesthetic agents. The illustration depicts a synaptic cleft between a presynaptic neuron, which releases GABA from vesicles, and a postsynaptic neuron. GABA binds to two types of receptors: synaptic GABA receptors, which increase postsynaptic currents, and extrasynaptic GABA receptors, which increase tonic current. The diagram highlights how specific anesthetics—Midazolam, Propofol, Thiopental, Sevoflurane, and Isoflurane—act as positive modulators (+) on both receptor types, particularly enhancing tonic current. Conversely, Dexmedetomidine and negative allosteric modulators of α5 GABAA receptors exert inhibitory effects (-) on these extrasynaptic pathways. The net increase in GABAergic inhibition and tonic current is linked via arrows to a mouse model labeled 'Cognitive dysfunction,' suggesting a clinical correlation between excessive GABAergic tonic signaling and impaired cognitive outcomes. This diagram serves as an educational tool for neuropharmacology and anesthesiology, focusing on GABA receptor distribution and drug-induced neurotoxicity.

An anatomical diagram of the human brain in a midsagittal view illustrating the dopamine hypothesis of schizophrenia. The illustration highlights two primary dopaminergic pathways originating from the Ventral Tegmental Area (VTA) in the midbrain: the Mesocortical Dopamine Pathway, represented by yellow arrows projecting to the prefrontal cortex, and the Mesolimbic Dopamine Pathway, indicated by yellow arrows projecting to the Nucleus Accumbens. Additionally, blue arrows indicate projections toward the Striatum. At the top, a conceptual comparison lists clinical correlations: 'Antipsychotics' are associated with reduced 'Dopaminergic activity' and 'Negative symptoms,' while 'Amphetamines' are linked to increased 'Dopaminergic activity' and 'Positive symptoms.' Vertical arrows between these lists indicate an inverse relationship between the effects of these substances. This diagram serves as a neurobiological model for medical students and clinicians to visualize the pathophysiology of schizophrenia and the mechanism of action for antipsychotic medications and psychostimulants.

This medical pathophysiology diagram illustrates the bidirectional relationship of the gut-brain axis in the context of schizophrenia. At the top, a brain illustration represents schizophrenia, listing primary clinical symptoms (hallucinations, delusions, catatonic behavior, etc.) and highlighting the 'dopamine disorder' and 'glutamate disorder' hypotheses. A circular flow connects the brain to the gastrointestinal tract (large intestine). The ascending 'Neuroactive Pathway Dysregulation' (red arrow) demonstrates how the gut influences the brain via microbial metabolites, the vagus nerve, the enteric nervous system, and key neurotransmitters including dopamine, serotonin, GABA, acetylcholine, and norepinephrine. Conversely, the descending pathway (blue arrow) illustrates the impact of schizophrenia management, noting that antipsychotic treatments can cause gut microbial dysbiosis and metabolic dysfunction. A detailed inset at the bottom shows the gut barrier with enteroendocrine cells and diverse microbiota, emphasizing the role of microbial diversity in systemic homeostasis. This infographic is designed for educational use in psychiatry and gastroenterology to explain neurobiological mechanisms and treatment side effects.

This pathophysiology diagram illustrates the neurobiological mechanism linking increased kynurenic acid (KYNA) levels to the pathogenesis of schizophrenia and psychosis across specific brain regions. In the Prefrontal Cortex (PFC), an astrocyte is shown producing KYNA, which acts as an antagonist at N-methyl-D-aspartate (NMDA) receptors. This interaction results in decreased NMDA receptor signaling on GABAergic interneurons. The subsequent reduction in inhibitory GABAergic output leads to disinhibition and increased glutamatergic activity of cortical pyramidal neurons (indicated by a '+' sign). This pyramidal neuron projects to the Ventral Tegmental Area (VTA), where it provides excitatory stimulation to dopaminergic neurons. This activation of the mesolimbic pathway causes excessive dopamine release in the Ventral Striatum (indicated by '↑↑↑ DOPAMINE'). The final outcome of this increased dopaminergic signaling is labeled as 'PSYCHOSIS'. The diagram highlights the complex interaction between the kynurenine pathway, glutamatergic signaling, and dopaminergic neurotransmission in psychiatric disorders.

Educational composite image illustrating an experimental approach to modeling Parkinson's disease using a rodent model. Left: A diagnostic flowchart outlines the methodological sequence from microelectrode implantation in the basal ganglia to the classification of treatment (Saline vs. Levodopa) using Linear Predictive Coding (LPC) coefficients derived from Local Field Potential (LFP) recordings. Top Right: A coronal diagnostic image of a mouse striatum (AP +0.1) using Tyrosine Hydroxylase (TH) immunostaining (red fluorescence). The image demonstrates unilateral dopamine depletion in the right hemisphere following 6-OHDA neurotoxin injection, characterized by a significant loss of red staining compared to the intact left hemisphere. Arrows indicate the electrode tracts of the 16-channel microelectrode array within the dorsal striatum. Bottom Right: A clinical photograph of an Omnetics microelectrode array, showing the structural configuration of the fine wire electrodes used for localized neural recording. This visual summary integrates pathophysiology, neuroanatomical histology, and biomedical engineering concepts relevant to movement disorder research.

This composite diagnostic image presents fMRI statistical maps and clinical outcome data illustrating brain activity responses to levodopa in Parkinson’s disease (PD) patients. The top section displays seven columns (a–g) of axial (z=5), coronal (y=-8), and sagittal (x=-22) brain slices focusing on the basal ganglia. Columns compare different analytical approaches using UPDRS-III subscores: (a) standard ON-OFF medication analysis (green), (b) total UPDRS-III, (c) midline, (d) hemibody, (e) akinesia, (f) rigidity, and (g) tremor. Yellow clusters indicate a positive correlation with the score ('in' approach), red clusters represent treatment effects when accounting for the score as a nuisance variable ('out' approach), and blue indicates anatomical overlap. Notably, total UPDRS-III and midline subscores show significant correlations (yellow) in the basal ganglia, while akinesia and hemibody scores reveal strong treatment-related sensitivity (red). Rigidity shows a unique overlap of both approaches. The bottom section contains a bar plot demonstrating clinical outcomes, showing significant reduction in UPDRS-III scores across all subscores (except tremor) when comparing 'Levodopa off' (solid blue) to 'Levodopa on' (hatched blue) states.

Educational figure illustrating dopamine (DA) denervation in the basal ganglia motor control circuit, using a mouse model (Pitx3Null) for Parkinson’s disease research. (A) Confocal sagittal brain section and overlay diagram: Red Tyrosine Hydroxylase (TH) stain indicates dopaminergic projections, while Green Fluorescent Protein (GFP) outlines basal ganglia structures. The diagram maps the direct pathway medium spiny neuron (dMSN) circuit from the cortex and thalamus to the substantia nigra reticulata (SNr), highlighting D1 receptor (D1R) involvement in behavior promotion. (B) High-magnification 3 μm confocal section of a wild-type (Pitx3WT) mouse striatum shows dense, uniform TH staining (red) across both dorsal and ventral regions, representing normal dopamine innervation. (C) Corresponding section from a Pitx3Null mouse shows a severe dorso-ventral gradient of DA loss; the dorsal striatum (outlined) exhibits >90% loss of TH staining, while some ventral innervation is preserved. (D, E) Clinical behavioral comparison photographs show Pitx3Null and WT mice in basal and L-dopa-treated states, correlating histological dopamine deficiency with motor performance and pharmacological response.

A pathophysiology diagram illustrating the opioid signaling pathways within corneal epithelial cells and sensory nerves. The diagram identifies endogenous opioids (Met-enkephalins, Leu-enkephalins, Beta-endorphins) produced by epithelial, inflammatory cells, and sensory nerves, alongside exogenous opioids like Morphine and Fentanyl. Key receptors shown on corneal cells include Mu (MOR), Delta (DOR), Kappa (KOR), and Opioid Growth Factor receptor (OGFr). Catabolic enzymes NEP and APN are depicted as mediators of opioid degradation, which can be inhibited by agents like PL265 (DENKIs). A critical educational focus is the dose-dependent effect of Naltrexone (NTX); low or intermittent dosages are linked to inhibitory growth signals and the 'rebound opioid effect' leading to analgesia, whereas high or sustained dosages trigger activator growth signals. The pathway concludes with the transmission of an analgesic signal from the corneal surface through sensory nerves to the brain, demonstrating the autocrine and paracrine mechanisms of ocular pain management and tissue homeostasis.

This composite educational image illustrates the selective opioid modulation of thalamic excitatory inputs to the dorsal medial striatum (DMS) in a mouse model. (a) Coronal brain section micrographs demonstrate Cre-dependent expression of ChR2-EYFP (cyan) in vGluT2-positive neurons of the medial thalamus (MThal) and their subsequent axonal projections into the striatum (Str). (b) A schematic diagram shows the experimental setup for optogenetic stimulation of MThal terminals while recording from medium spiny neurons (MSNs) in the DMS. Accompanying electrophysiological traces show that the mu-opioid receptor (MOR) agonist DAMGO significantly suppresses optically evoked excitatory postsynaptic currents (oEPSCs), an effect reversed by the antagonist naloxone (NLX). In contrast, the delta-opioid receptor (DOR) agonist DPDPE and its antagonist naltrindole show no significant effect on oEPSC amplitude. (c) A summary dot plot quantifies these findings, displaying a marked decrease in % baseline EPSC following DAMGO application, whereas DPDPE maintains levels near 100%. This illustrates that MORs, but not DORs, selectively gate the vGluT2+ thalamo-striatal pathway, providing insight into the neurocircuitry of pain and reward processing.

Table 2 Mechanism of action of the 8 newly approved antiepileptic drugs (AEDs) <table><thead><tr><th>AED</th><th>Mechanism of action</th></tr></thead><tbody><tr><td>Clobazam</td><td>Binding to benzodiazepine at the GABA_A ligand-gated chloride channel complex</td></tr><tr><td>Eslicarbazepine</td><td>Use-dependent blockage of voltage-sensitive sodium channels</td></tr><tr><td>Ezogabine</td><td>Positive allosteric modulator of KCNQ2-5; positive allosteric modulator of GABA_A receptors</td></tr><tr><td>Lacosamide</td><td>Slow inactivation of voltage-gated sodium channels; binds to CRMP-2</td></tr><tr><td>Perampanel</td><td>AMPA receptor antagonist</td></tr><tr><td>Pregabalin</td><td>Binding to the α2-δ protein subunit of voltage-gated calcium channels</td></tr><tr><td>Rufinamide</td><td>Use-dependent blockage of voltage-sensitive sodium channels</td></tr><tr><td>Vigabatrin</td><td>Inactivation of GABA transaminase</td></tr></tbody></table>

This pathophysiology diagram illustrates the four-stage mechanism of a voltage-gated sodium (Na+) ion channel embedded in a lipid bilayer, focusing on the mechanical and electrostatic changes during depolarization. (1) Resting: The channel's coiled helices are closed, maintaining an electrostatic insulating seal across the 10 nm membrane. (2) Moment of Threshold: An approaching membrane soliton (mechanical wave) exerts pressure, displacing helices and disrupting the electrical insulation. This allows Na+ ions to enter the pore and interact with hydrophilic, negatively charged interior surfaces. (3) Threshold Forces: Inward Na+ influx creates electrostatic attraction (red arrows) toward the intracellular space. Mechanical 'iris-like' opening and contraction occur, causing lateral membrane expansion (green arrows) and a net intracellular force vector (blue arrow). (4) Refractory: Positive charge equalization occurs on the intracellular side, leading to pore closure. The channel remains in a refractory state with localized Na+ accumulation until charges are cleared by diffusion, preventing immediate reactivation.