{"id":"28f45686-502e-5aed-9de6-b825091a3d40","stable_key":"1b599eb7-b22a-5fda-bcf0-9d92b5ae1311:gb-the-drug-named-for-gaba-binds-a-calcium-channel","predicate":"binds","statement":"Gabapentin is a novel anticonvulsant drug with a mechanism of action apparently dissimilar to that of other antiepileptic agents, the detergent-solubilized binding protein from pig cerebral cortex membranes was purified 1022-fold, the purified protein had an apparent subunit molecular weight of 130,000 and was heavily glycosylated, its partial N-terminal amino acid sequence EPFPSAVTIK was identical to that reported for the alpha2delta subunit of the L-type calcium channel, binding to cells transfected with alpha2delta complementary DNA was elevated more than 10-fold over controls, and tritiated gabapentin is the first pharmacological agent described that interacts with an alpha2delta subunit of a voltage-dependent calcium channel.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"fe9e3e87-5275-55d4-aeed-a2c232044151","mechanism_event_label":"The anticonvulsant designed as a GABA analogue turned out to bind a calcium channel subunit instead.","subject":{"id":"0f3999ad-42a1-5d99-88a5-f32cf0556715","slug":"gabapentin","display_name":"Gabapentin","entity_type_key":"drug"},"object":{"id":"74c59217-cda4-5a1f-be36-2657b7c8a196","slug":"cacna2d1","display_name":"The alpha-2-delta subunit of a voltage-dependent calcium channel","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"fe9e3e87-5275-55d4-aeed-a2c232044151","stable_key":"1b599eb7-b22a-5fda-bcf0-9d92b5ae1311:gb-the-drug-named-for-gaba-binds-a-calcium-channel-event","event_type":"biochemical_relationship","label":"The anticonvulsant designed as a GABA analogue turned out to bind a calcium channel subunit instead.","description":"Gabapentin is a novel anticonvulsant drug with a mechanism of action apparently dissimilar to that of other antiepileptic agents, the detergent-solubilized binding protein from pig cerebral cortex membranes was purified 1022-fold, the purified protein had an apparent subunit molecular weight of 130,000 and was heavily glycosylated, its partial N-terminal amino acid sequence EPFPSAVTIK was identical to that reported for the alpha2delta subunit of the L-type calcium channel, binding to cells transfected with alpha2delta complementary DNA was elevated more than 10-fold over controls, and tritiated gabapentin is the first pharmacological agent described that interacts with an alpha2delta subunit of a voltage-dependent calcium channel.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d5b98fa8-0612-5a5a-aa3c-6cfd8ff88867","slug":"gaba","display_name":"Gamma-aminobutyric acid","entity_type_key":"small_molecule"},"role":"namesake_molecule","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"37047e5b-5a63-5058-b01f-6eb41b8d70a4","slug":"brain-capillary-endothelium","display_name":"Brain capillary endothelial cells","entity_type_key":"cell_type"},"role":"unrelated_tissue","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"0f3999ad-42a1-5d99-88a5-f32cf0556715","slug":"gabapentin","display_name":"Gabapentin","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"74c59217-cda4-5a1f-be36-2657b7c8a196","slug":"cacna2d1","display_name":"The alpha-2-delta subunit of a voltage-dependent calcium channel","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/gaba-research/8621444.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"1723620d459b4f48ad397d59284df3f0619894ba82c6d066a42a47a0edb22216\", \"start_char\": 0, \"end_char\": 1531, \"text_sha256\": \"1723620d459b4f48ad397d59284df3f0619894ba82c6d066a42a47a0edb22216\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purification of a radioligand binding protein from pig cerebral cortex with N-terminal sequencing and expression in transfected cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Tritiated gabapentin binding, followed through a six-step purification to protein identity","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A binding and purification study. It identifies what the drug binds; it does not test the GABA receptors, so the absence of GABA-receptor binding is not measured here.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in.","comparator":null,"unit":null,"notes":"","entity":{"slug":"gaba","display_name":"Gamma-aminobutyric acid","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Pig and rat","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The anticonvulsant designed as a GABA analogue turned out to bind a calcium channel subunit instead.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[gb-p8621444] The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel. (1996). https://pubmed.ncbi.nlm.nih.gov/8621444/ DOI: 10.1074/jbc.271.10.5768","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cerebral cortex, heart and skeletal muscle","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"5e6d970a-1556-5d22-bb41-135cd31f6c6e","evidence_kind":"source_excerpt","locator":"Lines 300-311","start_line":300,"end_line":311,"excerpt":"### gb-the-drug-named-for-gaba-binds-a-calcium-channel\nGabapentin is a novel anticonvulsant drug with a mechanism of action apparently dissimilar to that of other antiepileptic agents, the detergent-solubilized binding protein from pig cerebral cortex membranes was purified 1022-fold, the purified protein had an apparent subunit molecular weight of 130,000 and was heavily glycosylated, its partial N-terminal amino acid sequence EPFPSAVTIK was identical to that reported for the alpha2delta subunit of the L-type calcium channel, binding to cells transfected with alpha2delta complementary DNA was elevated more than 10-fold over controls, and tritiated gabapentin is the first pharmacological agent described that interacts with an alpha2delta subunit of a voltage-dependent calcium channel.\nCondition category: normal\nnutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in.\nplain_language: The anticonvulsant designed as a GABA analogue turned out to bind a calcium channel subunit instead.\norganism: Pig and rat\ntissue_or_cell_type: Cerebral cortex, heart and skeletal muscle\nexperimental_model: Purification of a radioligand binding protein from pig cerebral cortex with N-terminal sequencing and expression in transfected cells\nlimitations: A binding and purification study. It identifies what the drug binds; it does not test the GABA receptors, so the absence of GABA-receptor binding is not measured here.\nexposure: Tritiated gabapentin binding, followed through a six-step purification to protein identity\nevidence_span: {\"source_cache\": \"artifacts/gaba-research/8621444.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"1723620d459b4f48ad397d59284df3f0619894ba82c6d066a42a47a0edb22216\", \"start_char\": 0, \"end_char\": 1531, \"text_sha256\": \"1723620d459b4f48ad397d59284df3f0619894ba82c6d066a42a47a0edb22216\"}\n[gb-p8621444] The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel. (1996). https://pubmed.ncbi.nlm.nih.gov/8621444/ DOI: 10.1074/jbc.271.10.5768","model_system":"Purification of a radioligand binding protein from pig cerebral cortex with N-terminal sequencing and expression in transfected cells","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [gb-p8621444] The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel. (1996). https://pubmed.ncbi.nlm.nih.gov/8621444/ DOI: 10.1074/jbc.271.10.5768","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"197c25bb-45fa-5e97-b3ab-2d2eff4e0d0a","stable_key":"import-1b599eb7-b22a-5fda-bcf0-9d92b5ae1311","title":"GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"07e36027ff70dbbe5563cddfa4758fd9b9b6eec148faecccafd476900b770456","revision_id":"a12d61de-f189-5bda-af3d-f31a1e61bccf","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}