Pethidine

6Node page

what any key link opens

psx:substance/pethidine/claim/dc9f6d47-39eb-4ae1-b456-7cb96b2fdb08

claim2026-05-10workinginconclusive

derived from · upstream

usedToxicity of norpethidine in sickle cell crisis.psx:substance/pethidine/src/pmid:1611370

feeds · downstream

informed_bysection/safety.full@1psx:substance/pethidine/section/safety.full@1

psx:substance/pethidine/claim/dc9f6d47-39eb-4ae1-b456-7cb96b2fdb08
├─ used  src/pmid:1611370  Toxicity of norpethidine in sickle cell crisis.
  ├─ informed_by  claim/556b0f14-ee9b-4098-88b6-ca42abc0d6b1  Claim in safety — inconclusive  working
  ├─ informed_by  claim/768b1a8b-b058-4da7-bef8-91e9eb8355fb  Claim in safety — supported
  ├─ informed_by  claim/612c1936-6189-483d-8f16-16efa035fa40  Claim in safety — inconclusive  working
  ├─ informed_by  claim/0f8475c9-8ab1-4704-8bdb-6d8f550ec63b  Claim in safety — inconclusive  working
  ├─ informed_by  claim/f4eb569f-49f2-4f52-8f2b-6457134132d4  Claim in safety — inconclusive  working
  ├─ informed_by  claim/81c012b7-a185-42ec-bdb2-aa49d9430099  Claim in safety — supported
  ├─ informed_by  claim/55df1db3-a73b-4cd5-b9d4-4251c09f9944  Claim in safety — supported
  ├─ informed_by  claim/1316c7db-cb72-4672-890a-dc06a57f2ba4  Claim in safety — supported
  ├─ informed_by  claim/ede8d820-a949-4a14-9631-1c587c352720  Claim in safety — inconclusive  working
  ├─ informed_by  claim/c1d91782-8da4-4cd8-9907-5dcef728a709  Claim in safety — supported
  ├─ informed_by  claim/591fe9e9-9f62-4598-9ba2-2974fa8e648e  Claim in safety — supported
  ├─ informed_by  claim/262d8c30-eb7e-4190-ba7f-e0d505954ea9  Claim in safety — supported
  ├─ informed_by  claim/38646d97-0fb6-46d4-b91a-a4f076b5bd75  Claim in safety — inconclusive  working
  ├─ informed_by  claim/87c9f3f2-e7d7-4194-ad6d-037f544f4eaf  Claim in safety — inconclusive  working
  ├─ informed_by  claim/30aa2e18-2135-481c-b267-69d6b87c595e  Claim in safety — inconclusive  working
  ├─ informed_by  claim/c93bd8e3-dd20-4d68-9255-91c8065bf7d0  Claim in safety — inconclusive  working
  ├─ informed_by  claim/07373dc7-9e90-46d3-bacb-30f4483b76c9  Claim in safety — inconclusive  working
  ├─ informed_by  claim/f376ead8-f037-4dde-99b8-753bb85cfda5  Claim in safety — supported
  ├─ informed_by  claim/834ba86c-1e58-46c2-9277-b775d6f912a6  Claim in safety — inconclusive  working
  ├─ informed_by  claim/a76f7040-cc42-46e9-81fa-0d55ff1401e6  Claim in safety — supported
  ├─ informed_by  claim/3286201e-9780-4366-a434-18a93cf31c2f  Claim in safety — supported
  ├─ informed_by  claim/0a394ff4-e3ba-48ed-a2af-6c417fc7f343  Claim in safety — inconclusive  working
  ├─ informed_by  claim/be9f8c88-0399-4b6d-8155-05121c284341  Claim in safety — supported
  ├─ informed_by  claim/a5c27c69-bb91-4bf7-bde2-d3e5fbb27e3b  Claim in safety — inconclusive  working
  ├─ informed_by  claim/c503c7b2-8d73-491b-871a-69c96f1815cc  Claim in safety — inconclusive  working
  ├─ informed_by  claim/959a0497-526f-40bc-965c-bdb7aca76c7a  Claim in safety — supported
    ├─ used  src/url:05970c7a69e0f448  Meperidine - StatPearls (NCBI Bookshelf)
    ├─ used  src/url:c32e7cf9949f2e0e  Pethidine pharmacology, pharmacokinetics, history, legal status
    ├─ used  src/doi:10.5812/aapm.119156  Full Opioid Agonists and Tramadol: Pharmacological and Clinical Considerations.
    ├─ used  src/pmid:9747665  Adverse effects of opioid agonists and agonist-antagonists in anaesthesia.
    ├─ used  src/pmid:6838077  Meperidine and central neurotoxicity.
    ├─ used  src/doi:10.1136/jnnp.52.12.1450  Norpethidine induced myoclonus in a patient with renal failure.
    ├─ used  src/doi:10.1111/jgs.18372  American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults.
    ├─ used  src/doi:10.1186/cc5709  Meperidine and skin surface warming additively reduce the shivering threshold: a volunteer study.
    ├─ used  src/doi:10.1002/14651858.cd009234.pub2  Pain management for women in labour: an overview of systematic reviews
    ├─ used  src/url:2526b8ac32790ba2  Lorazepam UK controlled drug classification
    ├─ used  src/url:e0da5e9df4cc35a1  Pethidine (CID 4058) - Chemical Identity
    ├─ used  src/url:328aec25ba6fb926  Meperidine chemical properties: CAS 57-42-1, SMILES, physical constants
    ├─ used  src/doi:10.1017/S146114570900011X
    ├─ used  src/doi:10.5812/hepatmon.32636  Opioid Drugs in Patients With Liver Disease: A Systematic Review
    ├─ used  src/doi:10.1016/j.apsb.2016.07.016  Insights into CYP2B6-mediated drug-drug interactions
    ├─ used  src/doi:10.1371/journal.pone.0102054  Chronopharmacodynamics and Chronopharmacokinetics of Pethidine in Mice
    ├─ used  src/doi:10.1186/s12871-020-01116-5  Effect of intrathecal lipophilic opioids on the incidence of shivering in women undergoing cesarean delivery after spinal anesthesia: a systematic review and bayesian network meta-analysis
    ├─ used  src/doi:10.1097/aln.0000000000000935  Practice Guidelines for Obstetric Anesthesia
    ├─ used  src/doi:10.1002/(sici)1097-0142(19991101)86:9<1856::aid-cncr30>3.0.co;2-g  Opioid rotation for cancer pain
    ├─ used  src/doi:10.1016/j.annemergmed.2007.09.033  Meperidine for Acute Sickle Cell Pain in the Emergency Department: Revisited Controversy
    ├─ used  src/doi:10.3390/ijms20174302  The Mechanisms Involved in Morphine Addiction: An Overview
    ├─ used  src/doi:10.2165/00002018-199513020-00004  The Serotonin Syndrome
    ├─ used  src/doi:10.52965/001c.39576  Clinically Relevant Drug Interactions with Monoamine Oxidase Inhibitors
    ├─ used  src/doi:10.1002/cncr.10389  The panorama of opioid-related cognitive dysfunction in patients with cancer
    ├─ derived_from  gen/6ab87bfa-42dd-4567-a5d4-592d608deea1  Generation — pipeline-v5
    ├─ generated_by  pub/b6918789-e0c8-47e1-96b1-c48aa2917dab  Publication — backfill
      ├─ used  search/dbd98f61-2a25-430b-ac0b-fe7baf01eed9  Searched PubChem for "pethidine"
      ├─ used  search/cd5be98f-671f-4242-aeb8-3cd1b43c75c1  Searched PubMed for "pethidine meperidine pharmacology receptor binding opioid"
      ├─ used  search/10207429-19a5-42d1-8015-f0584dcd0e9b  Searched OpenAlex for "meperidine pethidine opioid pharmacology"
      ├─ used  search/4b63c40f-85f4-4ab6-bbe9-a2cefddd888c  Searched OpenAlex for "meperidine pethidine serotonin syndrome MAOI interaction"
      ├─ used  search/20c856a7-0b68-42e2-87b0-e0c961367b08  Searched OpenAlex for "meperidine normeperidine seizure neurotoxicity accumulation"
      ├─ used  search/e4be72db-ae15-4ba9-86ff-c793fe436de3  Searched OpenAlex for "meperidine pethidine pharmacokinetics norpethidine metabolism CYP"
      ├─ used  search/e848b2e4-d6b3-423a-94e9-17de11e49545  Searched OpenAlex for "meperidine critical review clinical neurotoxicity normeperidine seizure"
      ├─ used  search/3607597c-d3f3-4c77-870d-568e2f043fe8  Searched OpenAlex for "pethidine labor pain obstetric analgesia neonatal effects"
      ├─ used  search/9732c8e6-7817-4a4f-9839-3aa6b107119c  Searched OpenAlex for "meperidine normeperidine seizure neurotoxicity accumulation renal failure"
      ├─ used  search/1a382d1d-9388-496f-9e9d-1a5aed5a122e  Searched UK Government for "pethidine controlled drugs classification UK"
      ├─ used  search/ca614c1e-58d7-4e04-b330-3a4b5b7a8fc3  Searched WebSearch for "pethidine meperidine DEA Schedule II legal status UK Misuse Drugs Act international scheduling"
      ├─ used  search/ad42a367-0e5c-4260-9864-1c4e493ee2db  Searched WebSearch for "pethidine meperidine discovery 1939 Eisleb Schaumann IG Farben first synthetic opioid history"
      ├─ used  search/39b002a9-6210-470f-bb08-dff96b0cd629  Searched HandWiki for "Pethidine pharmacology pharmacokinetics history legal status"
      ├─ used  search/ef0833bd-ad9e-48c4-8d9e-314d80ccbeae  Searched NCBI Bookshelf (StatPearls) for "meperidine pharmacology"
      ├─ used  search/528943a0-fc5a-44fa-baf0-b8cf0faf7ee7  Searched WebSearch for "meperidine pethidine 2023 Beers Criteria potentially inappropriate medications older adults avoid"
      ├─ used  search/4b8ec646-e827-4d5c-ba09-e2dae0a93ae8  Searched WebSearch for "meperidine pethidine SMILES canonical CAS number 57-42-1 physical properties melting point"
      ├─ used  search/8d7e8a34-529d-4e19-bf1a-68bac70a896e  Searched Multiple API and web sources for "Synthesis of pharmacological, pharmacokinetic, historical, safety, and legal data for research output"
      └─ used  search/c9b35da6-82d5-4da3-b555-ac0b571188c1  Searched Research output writing for "Write 01-research-output.md"
├─ informed_by  section/safety.full@1
  ├─ used  version/1  Revision 1
  ├─ used  claim/bd0f98e6-46bc-410f-90ed-3ca9a2e17b28  Claim in pharmacology — inconclusive  working
  ├─ used  claim/2f0c4024-25e0-43ea-93dd-b373720c855c  Claim in clinical-evidence — inconclusive  working
  ├─ used  claim/4bbeb3c8-01ae-4e8d-907f-f66b6b9beb8e  Claim in safety — inconclusive  working
  ├─ used  claim/e593ae3c-c76c-4f79-bdd5-e9c81d63e496  Claim in history — inconclusive  working
    ├─ derived_from  issue/notice@605e29df7ada  Issued notice
    ├─ derived_from  issue/info_card@cbd246c2f5fa  Issued info_card
    ├─ derived_from  issue/emergency@f85b2d2362c9  Issued emergency
    ├─ derived_from  issue/info_card@b1ea9c80087d  Issued info_card
    ├─ informed_by  section/pharmacology.full@1
    ├─ informed_by  section/clinical-evidence.full@1
    ├─ informed_by  section/history.full@1
      ├─ used  claim/5d8702e7-4e3c-431e-9b1a-735dc40e7c1d  Claim in summary — inconclusive  working
      ├─ used  claim/3bddee34-47d2-4037-aa63-b41000040b68  Claim in pharmacology — supported
      ├─ used  claim/102d1f03-8019-4bef-ae24-e5ccf15d4e56  Claim in pharmacology — supported
      ├─ used  claim/4051761c-e20b-42f6-8784-2e5fa57e5fdc  Claim in pharmacology — supported
      ├─ used  claim/804022f5-473c-4bf4-b46e-56731ea5c007  Claim in history — inconclusive  working
      ├─ used  claim/7216a097-cdd2-4e1d-85ef-d91d933e6e1b  Claim in chemistry — supported
      ├─ used  claim/426c6f07-2600-4255-8433-8fae965ecc89  Claim in receptor-pharmacology — inconclusive  working
      ├─ used  claim/3e659268-b908-4676-a213-c6998eec15e5  Claim in receptor-pharmacology — supported
      ├─ used  claim/b0f12bed-58bd-4f30-9417-bca39de34791  Claim in comparative-pharmacology — inconclusive  working
      ├─ used  claim/6884be1c-7309-43d7-afb1-d9cc2c3cba1c  Claim in summary — inconclusive  working
      ├─ used  claim/633042e2-f45b-479b-8d61-a05aefef0187  Claim in pharmacology — supported
      ├─ used  claim/b4a3fa63-5f0c-4d84-bdbe-2ddcbaf38177  Claim in pharmacology — inconclusive  working
      ├─ used  claim/b03ba901-fbca-4ade-87c4-45c455cb1077  Claim in pharmacology — supported
      ├─ used  claim/d9926be4-71ff-4699-8cb8-11f52c8684d0  Claim in pharmacology — supported
      ├─ used  claim/7ab55b5c-9c7c-4b01-ba57-8615a4119bcc  Claim in receptor-pharmacology — inconclusive  working
      ├─ used  claim/5ee99db9-d3e2-4c0e-bb7c-f393047d192e  Claim in receptor-pharmacology — supported
      ├─ used  claim/dbe614b8-3f1e-4c08-95ac-64915b2bc8e5  Claim in comparative-pharmacology — supported
      ├─ used  claim/22f991c9-0b5e-40dc-93c0-e5bc8de468c0  Claim in neuroscience — inconclusive  working
      ├─ used  claim/3457061b-a28c-46c8-8e17-b5a6ec090319  Claim in pharmacology — inconclusive  working
      ├─ used  claim/689a0a85-bf4a-459d-b897-d3f89020e940  Claim in summary — inconclusive  working
      ├─ used  claim/ee8978c0-9e6b-4972-8934-6aae932d56ae  Claim in history — inconclusive  working
      ├─ used  claim/59944756-46cc-449f-9ff2-e13b4c1f84cb  Claim in pharmacology — inconclusive  working
      ├─ used  claim/413dcc95-b967-4062-8bc1-3593a50882f6  Claim in clinical-evidence — inconclusive  working
      ├─ used  claim/ff8ab8cb-e902-4f9d-b169-ae651d6ad820  Claim in pharmacology — inconclusive  working
      ├─ used  claim/74667a3f-2cb0-42e5-b50f-afa3389fc706  Claim in summary — inconclusive  working
      ├─ used  claim/fc606fa3-36e8-4c05-93cb-b275687ed6d1  Claim in history — inconclusive  working
      ├─ used  claim/0390a102-a802-442a-b707-08931535fd14  Claim in pharmacokinetic-detail — inconclusive  working
      ├─ used  claim/7503c7df-066a-4f2b-8657-eb60d3c27981  Claim in history — supported
      ├─ used  claim/77b1be9c-1408-4a7b-a41d-838538449ccf  Claim in summary — supported
      ├─ used  claim/cbac860d-16fa-4721-8992-0b50269ea3b5  Claim in pharmacology — supported
      ├─ used  claim/5254cdfc-c6d9-48ca-af7e-e652e902b45c  Claim in clinical-evidence — supported
      ├─ used  claim/f4157dfb-c192-4dc4-87e5-0609b68e0d9f  Claim in pharmacology — inconclusive  working
      ├─ used  claim/68ba9544-144b-4113-99fa-75e626d041ea  Claim in history — supported
      ├─ used  claim/a2ca0bc5-c67d-4aa6-abb4-97288f105d71  Claim in receptor-pharmacology — inconclusive  working
      ├─ used  claim/f32cbcdb-a43f-4de3-8210-8937d69077d8  Claim in clinical-evidence — supported
      ├─ used  claim/8d5a29c4-c2f1-4aad-bedf-fc6476ff073e  Claim in history — inconclusive  working
      ├─ used  claim/018839a6-cc7b-47dc-a88e-e11cfaf24a0e  Claim in clinical-evidence — inconclusive  working
      ├─ used  claim/7ea1de29-1c72-4a44-a0ea-a08686abfd1f  Claim in pharmacology — supported
      ├─ used  claim/28549799-d7a0-4c7f-ae75-7ae38b7f1945  Claim in receptor-pharmacology — supported
      ├─ used  claim/e0b31071-a7b1-4edc-99f1-7842c4bee34d  Claim in comparative-pharmacology — supported
      ├─ used  claim/4e7821e4-e543-4adc-84d1-d0a6b0b228db  Claim in neuroscience — supported
      ├─ used  claim/b7d8ba24-0f47-490f-8733-684410e4ae50  Claim in pharmacology — inconclusive  working
      ├─ used  claim/aa7d1771-2eaf-46fd-958c-3275e2b29fff  Claim in pharmacology — inconclusive  working
      ├─ used  claim/147d4960-9b1a-4993-ae1b-c1cff10de08c  Claim in pharmacokinetic-detail — inconclusive  working
      ├─ used  claim/9ab8f735-77dc-44d6-972f-1102ac5dbe5d  Claim in pharmacokinetic-detail — inconclusive  working
      ├─ used  claim/5a91c3e4-f465-42a4-a873-54764892920f  Claim in pharmacology — inconclusive  working
      ├─ used  claim/51389898-0383-4a90-a605-48aa4446b744  Claim in pharmacokinetic-detail — inconclusive  working
      ├─ used  claim/5e3cf203-0957-4730-80e9-8780c7d9b332  Claim in pharmacokinetic-detail — inconclusive  working
      ├─ used  claim/d63ade44-538d-4609-8b0f-6a1ee43c6e49  Claim in neuroscience — supported
      ├─ used  claim/4f690c43-5066-494f-9cf0-63179a34aa84  Claim in pharmacokinetic-detail — supported
      ├─ used  claim/23fa8474-bc6f-4a69-a012-b216e7aa7cc1  Claim in clinical-evidence — supported
      ├─ used  claim/d72231f5-b7c7-4cef-8dd8-140328452bee  Claim in clinical-evidence — inconclusive  working
      ├─ used  claim/8de45daa-0094-4a24-83ab-d3c0904e1101  Claim in comparative-pharmacology — inconclusive  working
      ├─ used  claim/84062f36-b56a-4cda-999e-7bb541a4f358  Claim in clinical-evidence — inconclusive  working
      ├─ used  claim/8606f1e3-757d-43e7-8687-404fff8bbce6  Claim in clinical-evidence — inconclusive  working
      ├─ used  claim/8d65a134-0f70-4321-902e-4d4675beed08  Claim in neuroscience — inconclusive  working
      └─ used  claim/e97ac88b-63f8-4e4d-bb96-e27f23e18956  Claim in neuroscience — inconclusive  working
… closure truncated at 200 nodes

indented by distance from this node, not by parentage

1Provenance card

the boundary, as counts

Sources

2517 with DOI

6 strong · 13 moderate · 6 weak

Compilations

22026-05-10T18:49:07.477Z

pipeline-v5 · prompt hash not recorded — run predates 2026-09

Decisions

34last ruled 2026-06-04

0 awaiting a ruling

Issued documents

42026-10-19T20:33:34.671Z

notice · info card · emergency

Searches

181 with no results

queries and counts on the build

Claims checked

8835 supported

35 supported · 53 not

Correspondence

0received

consent field ships in Phase 4

Edges

266

derivations recorded for this entity

Complete over 25 sources, 2 compilations, and 34 decisions.Not here: the private journal (never).Working material — drafts, discards, unsupported claims — is listed below and readable on the working page.Cite: psychedex.org/substances/pethidine/archive

2Build

one panel per compilation run

generation run 2026-05-09

24 min failedmodel not recordedplan not recordedrun/d5522d5b…

research

no artifact

draft

no artifact

audit

no artifact

verify

no artifact

simplify

no artifact

publish

no artifact

Selection

results seen0

selected by the model0

consumed as sources25

Verification

claims checked0

supported0

partially supported0

not supported0

inconclusive0

record
seen / partial
working

The model's own caveats

none raised on this run

Reproduce

inputs: 25 source keys (listed under Sources)
plan: not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
model: not recorded
streams: none — agent transcripts are persisted from 2026-09 onward

generation run 2026-05-10

62 min completedmodel pipeline-v5plan not recordedrun/6a2c3b9d…

Selection

results seen140

selected by the model29

consumed as sources25

Verification

claims checked88

supported35

partially supported0

not supported0

inconclusive53

record
seen / partial
working

The model's own caveats

taper_silent
safety_note

Reproduce

inputs: 25 source keys (listed under Sources)
plan: not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
model: pipeline-v5
streams: none — agent transcripts are persisted from 2026-09 onward

18 searches — query, source, results, what was kept and why

18 searches for this run
#	source	query	seen	kept	rationale
1	OpenAlex	meperidine pethidine opioid pharmacology	10	—	—
2	OpenAlex	meperidine normeperidine seizure neurotoxicity accumulation	10	—	—
3	OpenAlex	pethidine labor pain obstetric analgesia neonatal effects	8	2	Relevant to clinical use in labor, adverse effects in neonates, and comparison with epidural
4	OpenAlex	meperidine pethidine serotonin syndrome MAOI interaction	10	4	Directly relevant to serotonin syndrome risk and MAOI interactions with pethidine
5	PubMed · absence	pethidine meperidine pharmacology receptor binding opioid	0	—	—
6	PubChem	pethidine	1	1	Primary source for verified chemical identity data
7	OpenAlex	meperidine pethidine pharmacokinetics norpethidine metabolism CYP	10	2	Directly relevant to pethidine metabolism via CYP2B6 and pharmacodynamic profile
8	OpenAlex	meperidine critical review clinical neurotoxicity normeperidine seizure	10	2	Both review articles specifically describe meperidine pharmacology including unique features vs other opioids
9	UK Government	pethidine controlled drugs classification UK	1	1	Official government source for legal classification
10	HandWiki	Pethidine pharmacology pharmacokinetics history legal status	1	3	Comprehensive single-source pharmacological reference
11	OpenAlex	meperidine normeperidine seizure neurotoxicity accumulation renal failure	10	4	All directly relevant to normeperidine neurotoxicity and pharmacokinetics
12	WebSearch	pethidine meperidine discovery 1939 Eisleb Schaumann IG Farben first synthetic opioid history	10	1	Historical data for discovery section
13	WebSearch	pethidine meperidine DEA Schedule II legal status UK Misuse Drugs Act international scheduling	10	2	Cross-referenced legal status across jurisdictions
14	WebSearch	meperidine pethidine SMILES canonical CAS number 57-42-1 physical properties melting point	10	3	Physical-chemical data for chemical identity section
15	WebSearch	meperidine pethidine 2023 Beers Criteria potentially inappropriate medications older adults avoid	10	1	Key safety-relevant clinical guideline
16	NCBI Bookshelf (StatPearls)	meperidine pharmacology	1	1	Current clinical reference
17	Multiple API and web sources	Synthesis of pharmacological, pharmacokinetic, historical, safety, and legal data for research output	27	1	Comprehensive coverage for research output document
18	Research output writing	Write 01-research-output.md	1	1	—

88 claims by section — every cited sentence, checked against its source

safety28 · 12 ok

Acute pethidine overdose produces the classical opioid triad of respiratory depression, decreased consciousness, and — in a notable departure from other opioids — mydriasis (not miosis) and tachycardia (not bradycardia) due to concurrent anticholinergic activitysupported
Notably does NOT cause miosis (unlike other opioids). Common adverse effects: nausea, vomiting, respiratory depression, constipation, addiction. aapm.119156
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
MAOI + pethidine: can produce hyperthermia, agitation, clonus, and death. The reaction may be excitatory (serotonin syndrome) or depressant (coma, respiratory failure, hypotension)supported
Serotonergic drugs including meperidine can cause serotonin syndrome when combined with MAOIs. 5-HT reuptake inhibitors are contraindicated. 001c.39576
MAOI + pethidine: can produce hyperthermia, agitation, clonus, and death. The reaction may be excitatory (serotonin syndrome) or depressant (coma, respiratory failure, hypotension)supported
Serotonin syndrome may result from coadministration of pethidine with MAOIs or SSRIs. pmid:9747665
SSRI + pethidine: serotonin syndrome risk documented; combination requires extreme cautionsupported
Tramadol and meperidine (not morphine) induce serotonin syndrome-like behaviors in SERT-deficient mice. s146114570900011x
Claim in safety — inconclusiveinconclusiveworking →
SERT-deficient mice demonstrate exaggerated serotonergic responses to meperidine, confirming the transporter-mediated mechanismsupported
Tramadol and meperidine (not morphine) induce serotonin syndrome-like behaviors in SERT-deficient mice. Exaggerated in SERT-/- mice. Response blocked by 5-HT1A antagonist WAY 100635. s146114570900011x
High-dose or prolonged use produces cognitive dysfunction and delirium — particularly in elderly patients, where pethidine is associated with higher delirium rates than alternative opioids.supported
Meperidine listed as PIM to always avoid in older adults due to neurotoxicity (normeperidine accumulation), delirium risk, ineffectiveness at oral doses, and availability of safer alternatives. jgs.18372
High-dose or prolonged use produces cognitive dysfunction and delirium — particularly in elderly patients, where pethidine is associated with higher delirium rates than alternative opioids.supported
Cognitive dysfunction from opioids in cancer; elevation of opioid metabolites (including normeperidine) in renal impairment contributes to cognitive dysfunction. cncr.10389
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
SSRIs combined with pethidine also produce serotonin syndrome, confirmed in both animal models and clinical reportssupported
Tramadol and meperidine (not morphine) induce serotonin syndrome-like behaviors in SERT-deficient mice. Exaggerated in SERT-/- mice. s146114570900011x
Claim in safety — inconclusiveinconclusiveworking →
MAOI use within 14 days — serotonin syndrome or severe CNS/respiratory depression; this is the single most dangerous contraindication in opioid pharmacologysupported
Serotonergic drugs including meperidine can cause serotonin syndrome when combined with MAOIs. 5-HT reuptake inhibitors are contraindicated. 001c.39576
MAOI use within 14 days — serotonin syndrome or severe CNS/respiratory depression; this is the single most dangerous contraindication in opioid pharmacologysupported
Serotonin syndrome may result from coadministration of pethidine with MAOIs or SSRIs. pmid:9747665
Claim in safety — inconclusiveinconclusiveworking →
Older adults — 2023 AGS Beers Criteria: always avoid; delirium risk, normeperidine toxicity, inefficacy at common oral dosessupported
Meperidine listed as PIM to always avoid in older adults due to neurotoxicity (normeperidine accumulation), delirium risk, ineffectiveness at oral doses, and availability of safer alternatives. jgs.18372
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Concurrent SSRI use — serotonin syndrome risksupported
Tramadol and meperidine (not morphine) induce serotonin syndrome-like behaviors in SERT-deficient mice. s146114570900011x
Claim in safety — inconclusiveinconclusiveworking →

pharmacology17 · 8 ok

Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Pethidine is a full agonist at the μ-opioid receptor (MOR), which mediates its primary analgesic, sedative, euphoric, and respiratory depressant effectssupported
Meperidine described as phenylpiperidine, mu-opioid receptor agonist. Common adverse effects: nausea, vomiting, respiratory depression, constipation, addiction. aapm.119156
μ-Opioid receptor agonism — full agonist activity producing analgesia, sedation, respiratory depression, euphoria, constipation, and physical dependencesupported
Meperidine described as phenylpiperidine, mu-opioid receptor agonist. Common adverse effects: nausea, vomiting, respiratory depression, constipation, addiction. aapm.119156
Claim in pharmacology — inconclusiveinconclusiveworking →
Serotonin transporter (SERT) inhibition — pethidine blocks serotonin reuptake, producing serotonin syndrome risk when combined with MAOIs or SSRIs; this property is shared with tramadol but absent from morphine, fentanyl, and most other clinical opioidssupported
Tramadol and meperidine (not morphine) induce serotonin syndrome-like behaviors in SERT-deficient mice. Exaggerated in SERT-/- mice. s146114570900011x
Serotonin transporter (SERT) inhibition — pethidine blocks serotonin reuptake, producing serotonin syndrome risk when combined with MAOIs or SSRIs; this property is shared with tramadol but absent from morphine, fentanyl, and most other clinical opioidssupported
Serotonin syndrome may result from coadministration of pethidine with MAOIs or SSRIs. pmid:9747665
Claim in pharmacology — inconclusiveinconclusiveworking →
Anticholinergic (atropine-like) activity — produces tachycardia (not bradycardia), mydriasis (not miosis), dry mouth, and urinary retention; pethidine notably does not cause pupil constriction, in contrast to virtually all other clinical opioidssupported
Notably does NOT cause miosis (unlike other opioids). aapm.119156
Anticholinergic (atropine-like) activity — produces tachycardia (not bradycardia), mydriasis (not miosis), dry mouth, and urinary retention; pethidine notably does not cause pupil constriction, in contrast to virtually all other clinical opioidssupported
has atropine-like effects on heart rate (unlike fentanyl analogues). pmid:9747665
Histamine release — causes vasodilation, pruritus, and hypotension; not seen with the fentanyl familysupported
Pethidine causes histamine release and myocardial depression... unlike fentanyl analogues. pmid:9747665
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
High-risk populations include patients with renal failure, cancer patients on high cumulative doses, sickle cell disease patients, and the elderly.supported
Meperidine listed as PIM to always avoid in older adults due to neurotoxicity (normeperidine accumulation), delirium risk. jgs.18372

clinical-evidence9 · 3 ok

Claim in clinical-evidence — inconclusiveinconclusiveworking →
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Subramani et al. (2020) conducted a systematic review and Bayesian network meta-analysis of intrathecal lipophilic opioids for shivering prevention during caesarean delivery under spinal anaesthesia, encompassing 21 randomised controlled trials (N = 1,433 patients)supported
Meta-analysis: IT meperidine significantly reduced shivering incidence (OR 0.12, 95%CrI 0.05-0.29) in cesarean delivery under spinal anesthesia. s12871-020-01116-5
Kimberger et al. (2007) conducted a volunteer study demonstrating that meperidine and skin surface warming additively reduce the shivering threshold, providing mechanistic confirmation that the anti-shivering effect operates through a central thermoregulatory mechanism (κ-opioid mediated) rather than simply raising core temperature.supported
Meperidine and skin warming each linearly lower vasoconstriction and shivering thresholds. Combination reduced shivering threshold to 33.8C with only mild sedation and no respiratory toxicity. cc5709
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Claim in clinical-evidence — inconclusiveinconclusiveworking →
The 2023 American Geriatrics Society Beers Criteria classified meperidine as a medication to always avoid in older adults, based on moderate-quality evidence with a strong recommendation against usesupported
Meperidine listed as PIM to always avoid in older adults due to neurotoxicity (normeperidine accumulation), delirium risk, ineffectiveness at oral doses, and availability of safer alternatives. Strong recommendation, moderate evidence. jgs.18372
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Claim in clinical-evidence — inconclusiveinconclusiveworking →

history7 · 2 ok

The 2023 AGS Beers Criteria classified it as a medication to always avoid in older adults.supported
2023 Beers Criteria update. Meperidine listed as PIM to always avoid in older adults. jgs.18372
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Pethidine retains limited clinical use in specific niches: treatment of postoperative and post-anaesthetic shivering (where its κ-opioid activity provides unique efficacy), and in some jurisdictions as a labour analgesic, though Cochrane evidence suggests inferior efficacy and more adverse effects compared to alternativessupported
Meperidine and skin warming each linearly lower vasoconstriction and shivering thresholds. cc5709
Claim in history — inconclusiveinconclusiveworking →

pharmacokinetic-detail6 · 1 ok

Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
A mouse pharmacokinetic study demonstrated significant 24-hour rhythms in both pethidine and normeperidine Cmax and AUC, with higher plasma concentrations during the dark (active) phasesupported
Significant 24-h rhythm in pethidine analgesia in mice. Cmax and AUC of pethidine and norpethidine higher during dark phase. journal.pone.0102054

receptor-pharmacology6 · 3 ok

Pethidine inhibits the serotonin transporter (SERT), an action confirmed both by serotonin syndrome induction in clinical settings and by exaggerated serotonergic responses in SERT-deficient micesupported
Tramadol and meperidine (not morphine) induce serotonin syndrome-like behaviors in SERT-deficient mice. Exaggerated in SERT-/- mice. s146114570900011x
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Pethidine exhibits anticholinergic activity that is clinically relevant: mydriasis (unique among common opioids), tachycardia, dry mouth, and urinary retention are directly attributable to muscarinic receptor antagonismsupported
Notably does NOT cause miosis (unlike other opioids). aapm.119156
Pethidine exhibits anticholinergic activity that is clinically relevant: mydriasis (unique among common opioids), tachycardia, dry mouth, and urinary retention are directly attributable to muscarinic receptor antagonismsupported
has atropine-like effects on heart rate (unlike fentanyl analogues). pmid:9747665

neuroscience5 · 2 ok

Claim in neuroscience — inconclusiveinconclusiveworking →
Circadian neuropharmacology: Mouse data demonstrate circadian variation in pethidine PK. Does time-of-day affect efficacy, toxicity threshold, or abuse potential in humans?supported
Significant 24-h rhythm in pethidine analgesia in mice. Cmax and AUC of pethidine and norpethidine higher during dark phase. journal.pone.0102054
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
SERT inhibition elevates synaptic serotonin concentrations in raphe-cortical projectionssupported
Tramadol and meperidine (not morphine) induce serotonin syndrome-like behaviors in SERT-deficient mice. Exaggerated in SERT-/- mice. Response blocked by 5-HT1A antagonist WAY 100635. s146114570900011x

summary5 · 1 ok

Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
The 2023 AGS Beers Criteria lists pethidine as a medication to always avoid in older adultssupported
2023 Beers Criteria update. Meperidine listed as PIM to always avoid in older adults due to neurotoxicity (normeperidine accumulation), delirium risk, ineffectiveness at oral doses, and availability of safer alternatives. Strong recommendation, moderate evidence. jgs.18372

comparative-pharmacology4 · 2 ok

Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Tramadol shares pethidine's dual mechanism of opioid agonism and serotonin reuptake inhibition, making both compounds unusual among clinical opioids in producing serotonin syndrome risksupported
Tramadol and meperidine (not morphine) induce serotonin syndrome-like behaviors in SERT-deficient mice. s146114570900011x
Fentanyl does not cause histamine releasesupported
Pethidine causes histamine release and myocardial depression... unlike fentanyl analogues. pmid:9747665
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →

chemistry1 · 1 ok

Pethidine is the prototype member of the 4-phenylpiperidine opioid analgesic class — a family defined by a phenyl ring attached at the 4-position of a piperidine ringsupported
Meperidine described as phenylpiperidine, mu-opioid receptor agonist. aapm.119156

3Sources

25 consumed · sorted by year · feeds = sections resting on it

Sources
year	source	tier	status	feeds
2024	Lorazepam UK controlled drug classificationUK Home Officeurl:2526b8ac32790ba2	weak	consumed	cited only
2024	Meperidine - StatPearls (NCBI Bookshelf)Preuss CV, et al.url:05970c7a69e0f448	weak	consumed	cited only
2024	Meperidine chemical properties: CAS 57-42-1, SMILES, physical constantsChemicalBookurl:328aec25ba6fb926	weak	consumed	cited only
2024	Pethidine (CID 4058) - Chemical IdentityPubChem · PubChem Database (NCBI)url:e0da5e9df4cc35a1	moderate	consumed	cited only
2023	American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults.American Geriatrics Society · Journal of the American Geriatrics Societydoi:10.1111/jgs.18372	strong	consumed	5 sections
2023	Pethidine pharmacology, pharmacokinetics, history, legal statusHandWiki Chemistryurl:c32e7cf9949f2e0e	weak	consumed	cited only
2022	Clinically Relevant Drug Interactions with Monoamine Oxidase InhibitorsEdinoff AN, Swinford CR, Odisho AS, Burroughs CR, Stark CW · Health Psychology Researchdoi:10.52965/001c.39576	moderate	consumed	1 section
2021	Full Opioid Agonists and Tramadol: Pharmacological and Clinical Considerations.Edinoff AN, Kaplan LA, Khan S, Petersen M, Sauce E, Causey CD, Cornett EM, Imani F, Moradi Moghadam O, Kaye AM, Kaye AD · Anesthesiology and Pain Medicinedoi:10.5812/aapm.119156	moderate	consumed	7 sections
2020	Effect of intrathecal lipophilic opioids on the incidence of shivering in women undergoing cesarean delivery after spinal anesthesia: a systematic review and bayesian network meta-analysisSubramani Y, Nagappa M, Kumar K, et al. · BMC Anesthesiologydoi:10.1186/s12871-020-01116-5	strong	consumed	1 section
2019	The Mechanisms Involved in Morphine Addiction: An OverviewListos J, Lupina M, Talarek S, Mazur AJ, Orzelska-Gorka J · International Journal of Molecular Sciencesdoi:10.3390/ijms20174302	moderate	consumed	2 sections
2016	Insights into CYP2B6-mediated drug-drug interactionsHedrich WD, Hassan HE, Wang H · Acta Pharmaceutica Sinica Bdoi:10.1016/j.apsb.2016.07.016	moderate	consumed	3 sections
2016	Opioid Drugs in Patients With Liver Disease: A Systematic ReviewSoleimanpour H, Safari S, Shahsavari Nia K, Sanaie S, Alavian SM · Hepatitis Monthlydoi:10.5812/hepatmon.32636	strong	consumed	3 sections
2015	Practice Guidelines for Obstetric AnesthesiaApfelbaum JL, Hawkins JL, Bateman B, et al. · Anesthesiologydoi:10.1097/aln.0000000000000935	moderate	consumed	1 section
2014	Chronopharmacodynamics and Chronopharmacokinetics of Pethidine in MiceZhang C, Yu Z, Li X, Xu Y, Liu D · PLoS ONEdoi:10.1371/journal.pone.0102054	moderate	consumed	2 sections
2012	Pain management for women in labour: an overview of systematic reviewsJones L, Othman M, Dowswell T, Alfirević Ž, Gates S · Cochrane Database of Systematic Reviewsdoi:10.1002/14651858.cd009234.pub2	strong	consumed	2 sections
2009	Tramadol and another atypical opioid meperidine have exaggerated serotonin syndrome behavioural effects, but decreased analgesic effects, in genetically deficient serotonin transporter (SERT) mice.Fox MA, Jensen CL, Murphy DL · The International Journal of Neuropsychopharmacologydoi:10.1017/s146114570900011x	strong	consumed	cited only
2008	Meperidine for Acute Sickle Cell Pain in the Emergency Department: Revisited ControversyBallas SK · Annals of Emergency Medicinedoi:10.1016/j.annemergmed.2007.09.033	moderate	consumed	2 sections
2007	Meperidine and skin surface warming additively reduce the shivering threshold: a volunteer study.Kimberger O, Ali SZ, Markstaller M, Zmoos S, Lauber R, Hunkeler C, Kurz A · Critical Caredoi:10.1186/cc5709	strong	consumed	4 sections
2002	The panorama of opioid-related cognitive dysfunction in patients with cancerLawlor PG · Cancerdoi:10.1002/cncr.10389	moderate	consumed	1 section
1999	Opioid rotation for cancer painMercadante S · Cancerdoi:10.1002/(sici)1097-0142(19991101)86:9<1856::aid-cncr30>3.0.co;2-g	moderate	consumed	3 sections
1998	Adverse effects of opioid agonists and agonist-antagonists in anaesthesia.Bowdle TA · Drug Safetypmid:9747665	moderate	consumed	6 sections
1995	The Serotonin SyndromeSporer KA · Drug Safetydoi:10.2165/00002018-199513020-00004	moderate	consumed	2 sections
1992	Toxicity of norpethidine in sickle cell crisis.Pryle BJ, Grech H, Stoddart PA, Carson R, O'Mahoney T, Reynolds F · BMJ (Clinical research ed.)pmid:1611370	weak	consumed	4 sections
1989	Norpethidine induced myoclonus in a patient with renal failure.Reutens DC, Stewart-Wynne EG · Journal of Neurology, Neurosurgery & Psychiatrydoi:10.1136/jnnp.52.12.1450	weak	consumed	5 sections
1983	Meperidine and central neurotoxicity.Hershey LA · Annals of Internal Medicinepmid:6838077	moderate	consumed	5 sections
—	Searched PubMed for "pethidine meperidine pharmacology receptor binding opioid" — no resultsabsence		no results	—

4Docket

one filing per activity — decisions, correspondence, reports

0012026-05-10revisionRevision 1
Initial LLM generation (v5 pipeline, wiki, prose phase)
psx:substance/pethidine/version/1
0022026-06-04proposal32 value proposals approved together
one review action inferred from a shared reviewer and instant — the graph records one activity per proposal
32 items in this filing
- contraindication · renal
- contraindication · other
- contraindication · age
- contraindication · hepatic
- contraindication · neurological
- contraindication · other
- contraindication · psychiatric
- contraindication · metabolic
- contraindication · other
- contraindication · respiratory
- contraindication · pregnancy_breastfeeding
- dose_tier · threshold
- dose_tier · light
- dose_tier · common
- dose_tier · strong
- dose_tier · heavy
- timeline · oral · onset
- timeline · oral · peak
- timeline · oral · plateau
- timeline · oral · resolution
- timeline · oral · afterglow
- toxicity
- dependence · full
- withdrawal
- tolerance
- dosage · oral
- duration · oral · onset
- duration · oral · peak
- duration · oral · offset
- duration · oral · total
- duration · oral · aftereffects
psx:substance/pethidine/proposal/contraindication/99199194-d83c-4f63-8c09-5ca9ee96e52d
0032026-06-04publicationPublication — backfill
psx:substance/pethidine/pub/b6918789-e0c8-47e1-96b1-c48aa2917dab

5Issued documents

what the notice, info card and emergency page said, by hash

Issued documents
document	content hash	issued	from version	superseded
info_card	b1ea9c80087d2a5893317bf4…	2026-10-19 20:33	Revision 1	current
emergency	f85b2d2362c98030e2585598…	2026-09-04 04:31	Revision 1	current
info_card	cbd246c2f5faf865808e7e68…	2026-09-04 04:31	Revision 1	superseded2026-10-19
notice	605e29df7ada7b4e996f1616…	2026-09-04 04:31	Revision 1	current

Pethidine

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