Path ID: DB01595_MESH_D004831_1

db01595-mesh-d004831-1

Concepts

Identifier Name Type
MESH:D009567 nitrazepam Drug
InterPro:IPR006028 Gamma-aminobutyric acid A receptor/Glycine receptor alpha GeneFamily
UniProt:P35498 sodium voltage-gated channel alpha subunit 1 Protein
GO:0019228 neuronal action potential BiologicalProcess
CL:0011005 GABAergic interneuron Cell
HP:0020219 Motor seizure PhenotypicFeature
MESH:D004831 Myoclonic seizure Disease

Relationships

NOTE: predicates are annotated in Biolink Model (v1.3.0)

Subject Predicate Object
Nitrazepam POSITIVELY REGULATES Gamma-Aminobutyric Acid A Receptor/Glycine Receptor Alpha
Nitrazepam REGULATES Sodium Voltage-Gated Channel Alpha Subunit 1
Sodium Voltage-Gated Channel Alpha Subunit 1 REGULATES Neuronal Action Potential
Neuronal Action Potential LOCATED IN Gabaergic Interneuron
Gabaergic Interneuron NEGATIVELY CORRELATED WITH Motor Seizure
Gamma-Aminobutyric Acid A Receptor/Glycine Receptor Alpha NEGATIVELY REGULATES Motor Seizure
Motor Seizure SUPERCLASS OF Myoclonic Seizure

Comment: The anticonvulsant properties of nitrazepam and other benzodiazepines may be in part or entirely due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors (https://en.wikipedia.org/wiki/Nitrazepam#Pharmacology), so both classes of targets have been annotated here. Although the parmachological action on UniProt:P35498 is unknown (https://go.drugbank.com/drugs/DB01595#BE0000141) it’s believed that reduced sodium currents due to mutations in the gene that codes for UniProt:P35498 may cause hyper-excitability in GABAergic inhibitory interneurons, which would lead to seizures. In mouse models, a dramatic loss of sodium current in hippocampal GABAergic inhibitory interneurons would mean hypofunction of inhibitory circuits, leading to hyperexcitability of neuronal networks and result in epilepsy seizures (https://pubmed.ncbi.nlm.nih.gov/16921370/).

Reference: