ArticleACS chemical neuroscience2011
The Discovery and Characterization of ML218: A Novel, Centrally Active T-Type Calcium Channel Inhibitor with Robust Effects in STN Neurons and in a Rodent Model of Parkinson's Disease.
Article in ACS chemical neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
49 citing papers in PubMed, 98 citations in OpenAlex.
- Chromatin topology control by a muscle-specific ribosomal protein.bioRxiv : the preprint server for biology · 2026Article
- Inhibition of CaV1.4 channels by CaV3 channel antagonists ML218 and Z944.The Journal of general physiology · 2026Article
- Therapeutic Potential of Calcium Channel Blockers in Neuropsychiatric, Endocrine and Pain Disorders.Cells · 2025Review
- Targeting the fundamentals for tremors: the frequency and amplitude coding in essential tremor.Journal of biomedical science · 2025Review
- CaThe Journal of biological chemistry · 2025Article
- Selective inhibition of T-type calcium channel preserves ischemic pre-conditioning mediated neuroprotection during cerebral ischemia reperfusion injury in diabetic mice.Metabolic brain disease · 2024Article
- Structural basis for human CaCell research · 2024Article
- A mitochondrial inside-out iron-calcium signal reveals drug targets for Parkinson's disease.Cell reports · 2023Article
- Direct Current Stimulation Modulates Synaptic Facilitation via Distinct Presynaptic Calcium Channels.International journal of molecular sciences · 2023Article
- Base-Promoted Intramolecular Addition of Vinyl Cyclopropanecarboxamides to Access Conformationally Restricted Aza[3.1.0]bicycles.Molecules (Basel, Switzerland) · 2023Article
- Gene editing to prevent ventricular arrhythmias associated with cardiomyocyte cell therapy.Cell stem cell · 2023Article
- T-type calcium channels as therapeutic targets in essential tremor and Parkinson's disease.Annals of clinical and translational neurology · 2023Review
- Graded spikes differentially signal neurotransmitter input in cerebrospinal fluid contacting neurons of the mouse spinal cord.iScience · 2023Article
- Multiple Calcium Channel Types with Unique Expression Patterns Mediate Retinal Signaling at Bipolar Cell Ribbon Synapses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- CaInternational journal of molecular sciences · 2022Review
- Steroidal Antagonists of Progesterone- and Prostaglandin EMolecular pharmacology · 2022Article
- Mechanisms underlying spontaneous phasic contractions and sympathetic control of smooth muscle in the rat caudal epididymis.Pflugers Archiv : European journal of physiology · 2021Article
- ML218 HCl Is More Efficient Than Capsaicin in Inhibiting Bacterial Antigen-Induced Cal 27 Oral Cancer Cell Proliferation.International journal of molecular sciences · 2021Article
- Role of L-Type Voltage-Gated Calcium Channels in Epileptiform Activity of Neurons.International journal of molecular sciences · 2021Article
- Altered Calcium Influx Pathways in Cancer-Associated Fibroblasts.Biomedicines · 2021Article
Corrections and comments
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Authors and funding
25 authors at 4 institutions in 1 country.
Funding
Abstract
T-type Ca(2+) channel inhibitors hold tremendous therapeutic potential for the treatment of pain, epilepsy, sleep disorders, essential tremor and other neurological disorders; however, a lack of truly selective tools has hindered basic research, and selective tools from the pharmaceutical industry are potentially burdened with intellectual property (IP) constraints. Thus, an MLPCN high-throughput screen (HTS) was conducted to identify novel T-type Ca(2+) channel inhibitors free from IP constraints, and freely available through the MLPCN, for use by the biomedical community to study T-type Ca(2+) channels. While the HTS provided numerous hits, these compounds could not be optimized to the required level of potency to be appropriate tool compounds. Therefore, a scaffold hopping approach, guided by SurflexSim, ultimately afforded ML218 (CID 45115620) a selective T-Type Ca(2+) (Ca(v)3.1, Ca(v)3.2, Ca(v)3.3) inhibitor (Ca(v)3.2, IC(50) = 150 nM in Ca(2+) flux; Ca(v)3.2 IC(50) = 310 nM and Ca(v)3.3 IC(50) = 270 nM, respectively in patch clamp electrophysiology) with good DMPK properties, acceptable in vivo rat PK and excellent brain levels. Electrophysiology studies in subthalamic nucleus (STN) neurons demonstrated robust effects of ML218 on the inhibition of T-Type calcium current, inhibition of low threshold spike and rebound burst activity. Based on the basal ganglia circuitry in Parkinson's disease (PD), the effects of ML218 in STN neurons suggest a therapeutic role for T-type Ca(2+) channel inhibitors, and ML218 was found to be orally efficacious in haloperidol-induced catalepsy, a preclinical PD model, with comparable efficacy to an A(2A) antagonist, a clinically validated PD target. ML218 proves to be a powerful new probe to study T-Type Ca(2+) function in vitro and in vivo, and freely available.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.