{"id":"dc26fe68-6796-5c58-96ea-5c9019018507","stable_key":"c953cca8-774f-596d-b27a-f13c2c0b5fce:dhc-equal-conduction-block","predicate":"reported_comparison","statement":"In the efficacy sequence for inhibition of compound action potentials the order was capsaicin equal to dihydrocapsaicin, then capsiate, eugenol, guaiacol, zingerone, vanillin and vanillylamine, with capsaicin ten-fold more effective than procaine; the extent of inhibition is determined by the property of the side chain bound to the vanillyl group.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"d27ed594-8c34-5730-9eb7-78a33cf47e29","mechanism_event_label":"For blocking nerve conduction the two compounds are equally strong, and stronger than a local anaesthetic.","subject":{"id":"6259a8e0-9611-5f60-9e1b-53bbd8eb1afd","slug":"dihydrocapsaicin","display_name":"Dihydrocapsaicin","entity_type_key":"small_molecule"},"object":{"id":"9cdd3a64-5185-5998-82a6-d25c8409b998","slug":"capsaicin","display_name":"Capsaicin","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"d27ed594-8c34-5730-9eb7-78a33cf47e29","stable_key":"c953cca8-774f-596d-b27a-f13c2c0b5fce:dhc-equal-conduction-block-event","event_type":"observed_intervention","label":"For blocking nerve conduction the two compounds are equally strong, and stronger than a local anaesthetic.","description":"In the efficacy sequence for inhibition of compound action potentials the order was capsaicin equal to dihydrocapsaicin, then capsiate, eugenol, guaiacol, zingerone, vanillin and vanillylamine, with capsaicin ten-fold more effective than procaine; the extent of inhibition is determined by the property of the side chain bound to the vanillyl group.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b292933d-336b-5ce3-b773-9ea377bb31f3","slug":"compound-action-potential","display_name":"Fast-conducting compound action potential in peripheral nerve","entity_type_key":"cellular_process"},"role":"measured_endpoint","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"4b9c1b2b-630e-56f9-bdc9-67c8f36e9230","slug":"procaine","display_name":"Procaine, a local anaesthetic","entity_type_key":"chemical_species"},"role":"reference_compound","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7f3c783b-41b0-5f2b-ada9-344a5f8b5624","slug":"capsiate","display_name":"Capsiate, a non-pungent capsinoid ester","entity_type_key":"chemical_species"},"role":"weaker_analogue","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"6259a8e0-9611-5f60-9e1b-53bbd8eb1afd","slug":"dihydrocapsaicin","display_name":"Dihydrocapsaicin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"9cdd3a64-5185-5998-82a6-d25c8409b998","slug":"capsaicin","display_name":"Capsaicin","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/dihydrocapsaicin-research/23352977.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8a2b1f1a1bde0cfc3d08340f1951d88fb3711df6a40634a8c4c7bac63f8384bb\", \"start_char\": 0, \"end_char\": 1707, \"text_sha256\": \"8a2b1f1a1bde0cfc3d08340f1951d88fb3711df6a40634a8c4c7bac63f8384bb\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Compound action potentials recorded from frog sciatic nerve fibres by the air-gap method","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Capsaicin, dihydrocapsaicin, capsiate, eugenol, guaiacol, zingerone, vanillin, vanillylamine, vanillic acid, olvanil and curcumin, against procaine","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"An isolated nerve preparation with a clean negative control for the receptor: capsazepine did not block the effect and resiniferatoxin, a more powerful TRPV1 agonist, had none. That makes this a non-TRPV1 action of both compounds.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin.","comparator":null,"unit":null,"notes":"","entity":{"slug":"dihydrocapsaicin","display_name":"Dihydrocapsaicin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Frog","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"For blocking nerve conduction the two compounds are equally strong, and stronger than a local anaesthetic.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dhc-p23352977] Inhibition by capsaicin and its related vanilloids of compound action potentials in frog sciatic nerves. (2013). https://pubmed.ncbi.nlm.nih.gov/23352977/ DOI: 10.1016/j.lfs.2013.01.011","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Sciatic nerve","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"5fa5f721-f42e-59bc-a972-4f281d8327e9","evidence_kind":"source_excerpt","locator":"Lines 114-125","start_line":114,"end_line":125,"excerpt":"### dhc-equal-conduction-block\nIn the efficacy sequence for inhibition of compound action potentials the order was capsaicin equal to dihydrocapsaicin, then capsiate, eugenol, guaiacol, zingerone, vanillin and vanillylamine, with capsaicin ten-fold more effective than procaine; the extent of inhibition is determined by the property of the side chain bound to the vanillyl group.\nCondition category: normal\nnutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin.\nplain_language: For blocking nerve conduction the two compounds are equally strong, and stronger than a local anaesthetic.\norganism: Frog\ntissue_or_cell_type: Sciatic nerve\nexperimental_model: Compound action potentials recorded from frog sciatic nerve fibres by the air-gap method\nlimitations: An isolated nerve preparation with a clean negative control for the receptor: capsazepine did not block the effect and resiniferatoxin, a more powerful TRPV1 agonist, had none. That makes this a non-TRPV1 action of both compounds.\nexposure: Capsaicin, dihydrocapsaicin, capsiate, eugenol, guaiacol, zingerone, vanillin, vanillylamine, vanillic acid, olvanil and curcumin, against procaine\nevidence_span: {\"source_cache\": \"artifacts/dihydrocapsaicin-research/23352977.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8a2b1f1a1bde0cfc3d08340f1951d88fb3711df6a40634a8c4c7bac63f8384bb\", \"start_char\": 0, \"end_char\": 1707, \"text_sha256\": \"8a2b1f1a1bde0cfc3d08340f1951d88fb3711df6a40634a8c4c7bac63f8384bb\"}\n[dhc-p23352977] Inhibition by capsaicin and its related vanilloids of compound action potentials in frog sciatic nerves. (2013). https://pubmed.ncbi.nlm.nih.gov/23352977/ DOI: 10.1016/j.lfs.2013.01.011","model_system":"Compound action potentials recorded from frog sciatic nerve fibres by the air-gap method","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [dhc-p23352977] Inhibition by capsaicin and its related vanilloids of compound action potentials in frog sciatic nerves. (2013). https://pubmed.ncbi.nlm.nih.gov/23352977/ DOI: 10.1016/j.lfs.2013.01.011","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"263a8425-969d-5a1b-8a9b-6101ba6a26a7","stable_key":"import-c953cca8-774f-596d-b27a-f13c2c0b5fce","title":"Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21)","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":"97d90ff5dc65dc321068c3e2a0525585f32b2e17eb0c6bfa0d9ef26dc2d6c5a3","revision_id":"dbdc1ad7-a05a-579d-b2aa-c4348e3efc40","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"b181c02f-95d8-5a7f-b568-c648b4f8a4ff","title":"Does dihydrocapsaicin behave like capsaicin?","kind":"context_difference","status":"open","why":"Four studies in this collection measured the two compounds against each other and do not give one answer. On hypothermia in rats, dihydrocapsaicin was about 65% more effective than capsaicin. On block of nerve conduction in frog sciatic nerve they were exactly equal, at the top of a sequence of eleven vanilloids. On platelet aggregation they diverged by agonist: capsaicin inhibited both ADP-induced and arachidonic-acid-induced aggregation, dihydrocapsaicin only the latter. On human endothelial cells dihydrocapsaicin was the more cytotoxic of the two, killing at 100 micromolar where capsaicin needed 500. The answer is therefore endpoint-specific, and no record here explains why the saturated side chain matters for some endpoints and not others. This is the reason the two are kept as separate entities in this ledger rather than merged: a single merged compound could not carry four different answers.","resolution":"Unresolved; needs review.","created_at":"2026-09-22 03:40:20","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/b181c02f-95d8-5a7f-b568-c648b4f8a4ff","sides":[{"conflict_id":"b181c02f-95d8-5a7f-b568-c648b4f8a4ff","ordinal":0,"label":"For blocking nerve conduction the two compounds are equally strong, and stronger than a local anaesthetic.","revision_id":"dbdc1ad7-a05a-579d-b2aa-c4348e3efc40","start_line":114,"end_line":125,"quote":"### dhc-equal-conduction-block\nIn the efficacy sequence for inhibition of compound action potentials the order was capsaicin equal to dihydrocapsaicin, then capsiate, eugenol, guaiacol, zingerone, vanillin and vanillylamine, with capsaicin ten-fold more effective than procaine; the extent of inhibition is determined by the property of the side chain bound to the vanillyl group.\nCondition category: normal\nnutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin.\nplain_language: For blocking nerve conduction the two compounds are equally strong, and stronger than a local anaesthetic.\norganism: Frog\ntissue_or_cell_type: Sciatic nerve\nexperimental_model: Compound action potentials recorded from frog sciatic nerve fibres by the air-gap method\nlimitations: An isolated nerve preparation with a clean negative control for the receptor: capsazepine did not block the effect and resiniferatoxin, a more powerful TRPV1 agonist, had none. That makes this a non-TRPV1 action of both compounds.\nexposure: Capsaicin, dihydrocapsaicin, capsiate, eugenol, guaiacol, zingerone, vanillin, vanillylamine, vanillic acid, olvanil and curcumin, against procaine\nevidence_span: {\"source_cache\": \"artifacts/dihydrocapsaicin-research/23352977.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8a2b1f1a1bde0cfc3d08340f1951d88fb3711df6a40634a8c4c7bac63f8384bb\", \"start_char\": 0, \"end_char\": 1707, \"text_sha256\": \"8a2b1f1a1bde0cfc3d08340f1951d88fb3711df6a40634a8c4c7bac63f8384bb\"}\n[dhc-p23352977] Inhibition by capsaicin and its related vanilloids of compound action potentials in frog sciatic nerves. (2013). https://pubmed.ncbi.nlm.nih.gov/23352977/ DOI: 10.1016/j.lfs.2013.01.011","source_key":"import-c953cca8-774f-596d-b27a-f13c2c0b5fce","source_title":"Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21)","claim_ids":["dc26fe68-6796-5c58-96ea-5c9019018507"]},{"conflict_id":"b181c02f-95d8-5a7f-b568-c648b4f8a4ff","ordinal":1,"label":"Capsaicin blocks clumping triggered two ways; dihydrocapsaicin blocks only one of them.","revision_id":"dbdc1ad7-a05a-579d-b2aa-c4348e3efc40","start_line":153,"end_line":164,"quote":"### dhc-platelet-divergence\nCapsaicin, N-oleoyldopamine and N-arachidonoyl-dopamine inhibited ADP-induced platelet aggregation in a concentration-dependent manner, while arachidonic-acid-induced aggregation was inhibited by capsaicin, dihydrocapsaicin and N-arachidonoyl-dopamine but not by N-oleoyldopamine, and collagen-induced aggregation was inhibited only by the endogenous vanilloids and not by capsaicin or dihydrocapsaicin.\nCondition category: normal\nnutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin.\nplain_language: Capsaicin blocks clumping triggered two ways; dihydrocapsaicin blocks only one of them.\norganism: Human\ntissue_or_cell_type: Platelets\nexperimental_model: In-vitro human platelet aggregation with agonist-specified stimulation and an LDH viability control\nlimitations: The agonist-by-agonist design is what makes this useful: it separates the two plant compounds where a single-agonist study would have merged them. A TRPV1 antagonist control was included.\nexposure: Capsaicin and dihydrocapsaicin against the endogenous vanilloids N-oleoyldopamine and N-arachidonoyl-dopamine, with ADP, collagen and arachidonic acid as agonists\nevidence_span: {\"source_cache\": \"artifacts/dihydrocapsaicin-research/24953906.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8d11f6733abf59c36bf8e2b6ed6f44f759cab3fdd209ff3c84c21b20e178a717\", \"start_char\": 0, \"end_char\": 1870, \"text_sha256\": \"8d11f6733abf59c36bf8e2b6ed6f44f759cab3fdd209ff3c84c21b20e178a717\"}\n[dhc-p24953906] Vanilloid-like agents inhibit aggregation of human platelets. (2014). https://pubmed.ncbi.nlm.nih.gov/24953906/ DOI: 10.1016/j.thromres.2014.05.038","source_key":"import-c953cca8-774f-596d-b27a-f13c2c0b5fce","source_title":"Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21)","claim_ids":["252e11c5-a4e9-5561-9a2e-f8321900602b"]}]}],"corrections":[],"research":null}