Trimethobenzamide
antiemetic acting at the chemoreceptor trigger zone; ATC group aminoalkyl ethers [4]
Also sold as Tigan, Tebamide.
Findings for this medication
Research about this medication, graded for how strongly each finding can be attributed to it. Nothing here describes your own levels.
Trimethobenzamide has no documented classical depletion machinery in the sources opened. The label extractions [1][2][3] describe a short half-life (7 to 9 hours), 30 to 50 percent of a dose excreted unchanged in urine over 48 to 72 hours, an oxidative metabolite (trimethobenzamide N-oxide) named in one extraction [2], and no statement of CYP450 induction or inhibition, chelation, renal tubular wasting, or any vitamin, mineral, iron, copper, methemoglobin, hemolysis, antacid or food interaction. The only interaction in the label text is with alcohol. No red or orange entry is supported; both tiers are empty, and that is a finding, not an omission. No class extrapolation is graded in this dossier: trimethobenzamide was in no class-level cohort that was opened, and no stand-in drug was used.
antiemetic acting at the chemoreceptor trigger zone; ATC group aminoalkyl ethers [4] · ATC R06AA10 [4] · also sold as Tigan [1]; Tebamide (reference page only [6]); generic capsules and injection [5] · reviewed 2026-10-06. This describes research about the medication. It does not say anything about your own levels or health.
How to read the evidence grades
These colours describe how strongly a finding can be attributed to the medication in the research. They are not a severity score and they say nothing about your own health.
Grades describe how strongly a finding can be attributed to Trimethobenzamide in the research — not how common it is, how serious it would be, and not anything about you personally.
- Red — Severe
- Two or more independent Tier A sources, this drug in the cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
- Orange — Moderate
- At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit.
- Yellow — Low
- Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction.
- Not graded — disclosed evidence gap
- Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result.Source definition: Not gradeable under the rules above because nothing has been measured. Published as a documented gap, never as reassurance that there is no effect.
What the research found
Electrolytes and fluid (sodium, potassium): disease-effect context flag; the label direction is illness to drug risk, not drug to nutrient loss
Yellow — LowEvidence: / context flag
The label states that CNS reactions to trimethobenzamide have been reported during acute febrile illness, gastroenteritis, dehydration and electrolyte imbalance, and that restoration of body fluids and electrolyte balance is the primary emphasis; no study measured an electrolyte in trimethobenzamide users.
Full detail and limits
Electrolytes and fluid (sodium, potassium): disease-effect context flag; the label direction is illness to drug risk, not drug to nutrient loss
Yellow — LowWhat the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow / context flag
Limits on what this shows
- Null / negative: No tubular, aldosterone or antidiuretic-hormone effect is stated in any label extraction; no hyponatremia, SIADH or hypokalemia statement was returned in the three extractions (extraction prompts asked about electrolytes). Drug-attributable diarrhea or cramping cannot be separated from the illness being treated (Hard Rule 6).
- At-risk subgroups: People treated for gastroenteritis with ongoing vomiting or diarrhea, febrile or dehydrated patients, the elderly, and patients with reduced renal function (dose adjustment advised at creatinine clearance of 70 or less) [1]. These are risk groups for the illness-related disturbance and for drug accumulation, not for a drug-induced depletion.
Regulatory status
Label Warnings (as extracted): "During the course of acute febrile illness, encephalitides, gastroenteritis, dehydration and electrolyte imbalance" CNS reactions such as opisthotonos, convulsions, coma and extrapyramidal symptoms "have been reported"; Precautions: "Primary emphasis should be directed toward restoration of body fluids and electrolyte balance" [1]. The capsule renderings carry a caution during acute febrile illness and electrolyte imbalance [2] and during acute febrile illness and gastroenteritis [3]. Diarrhea and muscle cramps appear in the adverse-reaction list without frequency [1][2][3]. The label does not state that trimethobenzamide lowers or raises any electrolyte.
Population evidence
None. A Crossref title search pairing trimethobenzamide with sodium, potassium and electrolyte terms returned 15 records, none involving trimethobenzamide [13]. Crossref title listings of the drug itself (summarizer reported 61 records, 40 titles shown) include only titles on efficacy, formulation, extrapyramidal reactions in a neonate, hepatitis, immunoassay cross-reaction and teratogenicity in animals; none was opened and none concerns an electrolyte [8].
Mechanism
Named for the label direction only: dehydration and electrolyte disturbance from the underlying illness are described as settings in which the drug's CNS reactions occur [1]. No mechanism links the drug itself to renal or gastrointestinal electrolyte loss. Vomiting and diarrhea from the illness are a disease effect (Hard Rule 2).
Counter-evidence held on record
Counter-evidence on record Direction check (Hard Rule 4): the documented relationship is illness-related electrolyte and fluid disturbance raising the risk of the drug's CNS reactions, not the drug disturbing electrolytes. Confounding by indication is presumed: the drug is given to people who are already vomiting. Shares its label source with Oxygen delivery/utilization; see the Overlap map. Framing caution This is a disease effect and a label caution, not a nutrient depletion caused by this drug. It does not imply that sodium, potassium or other supplements are indicated. Fluid and electrolyte replacement during vomiting or diarrhea is managed clinically for the illness itself.
The five body-system areas
Each finding is counted once, in a single area. Where a study is mentioned in a second area it is context only.
Mitochondrial Burden
Each finding below is counted once, in this area only.
Mitochondrial burden
Not graded — disclosed evidence gapSee study details
No study of mitochondrial structure, membrane potential, electron transport or biogenesis with trimethobenzamide was found.
Full detail and limits
Mitochondrial burden
Not graded — disclosed evidence gapWhat the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded
Limits on what this shows
- Why no grade: Dual condition met: no Tier B or C evidence located (no in vitro, animal or human mitochondrial study of trimethobenzamide, and no class-level cohort naming it was opened), and no circulating mitochondrial-damage claim for trimethobenzamide located. The label extractions contain no mitochondrial statement [1][2][3].
Channels tried
Crossref title search "trimethobenzamide mitochondria oxidative stress respiration": 20 records, none naming trimethobenzamide [9]. Repair pass: Crossref "trimethobenzamide mitochondrial membrane potential toxicity": 14 records, only two named trimethobenzamide, both USP compendial monographs; the rest were unrelated membrane-potential papers and supplement files, including a computational mitochondrial-toxicity paper whose supplement could not be checked for this drug [27]. PubMed term listing "trimethobenzamide mitochondria": 9 records, all unrelated (PubMed split the term into "tri" plus mitochondria) [22]. PubMed listing of the drug itself, 114 records: no mitochondrial title in the pages read [21]. Label text [1][2][3]. Europe PMC and OpenAlex search: blocked. Tox21 mitochondrial membrane potential screening supplements were not reachable.
Gap type
Probable genuine gap, partly tooling-limited; not confirmed. Re-check with: Tox21 mitochondrial membrane potential assay data for trimethobenzamide, complex I, oxygen consumption, Tigan.
Oxidative Stress
Each finding below is counted once, in this area only.
Oxidative stress
Not graded — disclosed evidence gapSee study details
No study of reactive oxygen species, lipid peroxidation, glutathione or antioxidant enzymes with trimethobenzamide was found.
Full detail and limits
Oxidative stress
Not graded — disclosed evidence gapWhat the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded
Limits on what this shows
- Why no grade: Dual condition met: no Tier B or C evidence located and no circulating oxidative-stress or antioxidant-depletion claim for trimethobenzamide located. The label extractions contain no redox statement [1][2][3]. No class-level redox study naming trimethobenzamide in its cohort was opened, and none was assumed.
Channels tried
Same Crossref mitochondria and oxidative-stress title search [9] (no trimethobenzamide record). Repair pass: Crossref "trimethobenzamide glutathione reactive metabolite antiemetic": 15 records, eight named trimethobenzamide, all clinical antiemetic, analytical (RP-UPLC), compendial or the 1988 hypophagia report, none redox [28]; PubMed term listing "trimethobenzamide oxidative stress": 10 records, all unrelated "tri-" compounds [23]. Label text [1][2][3]. Terms covered: oxidative stress, reactive oxygen species, glutathione, reactive metabolite. Not reachable: malondialdehyde and antioxidant-enzyme abstract searches beyond the listing above.
Gap type
Probable genuine gap, partly tooling-limited; not confirmed.
Copper and Iron Balance
Copper and iron are assessed separately. Nothing here is counted twice.
Copper
Not graded — disclosed evidence gapSee study details
No study of serum copper, ceruloplasmin or copper-dependent enzyme activity in trimethobenzamide-exposed subjects was found.
Full detail and limits
Copper
Not graded — disclosed evidence gapWhat the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded
Limits on what this shows
- Why no grade: Dual condition met: no Tier B or C evidence located and no circulating copper claim for trimethobenzamide located. The label extractions state that copper is not mentioned [1][2][3] and describe no chelation or mineral interaction.
Channels tried
Crossref title search "trimethobenzamide iron copper zinc vitamin deficiency serum": 15 records, all micronutrient papers with no trimethobenzamide record [12]. Repair pass: PubMed term listing "trimethobenzamide copper": 10 records, all copper coordination chemistry or unrelated, none about trimethobenzamide [25]. A second Crossref phrasing (ceruloplasmin, ferritin, serum copper) returned HTTP 429 and was not read. Label text [1][2][3] and the Drugs.com interaction page [7] (no copper content).
Gap type
Probable genuine gap, partly tooling-limited; not confirmed.
Iron
Not graded — disclosed evidence gapSee study details
No study of serum iron, ferritin, transferrin saturation or iron absorption in trimethobenzamide-exposed subjects was found.
Full detail and limits
Iron
Not graded — disclosed evidence gapWhat the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded
Limits on what this shows
- Why no grade: Dual condition met: no Tier B or C evidence located and no circulating iron claim for trimethobenzamide located. The label extractions state that iron is not mentioned [1][2][3]; the labeled blood dyscrasias are an outcome and are handled in the Oxygen delivery/utilization entry, not as an iron finding (Hard Rule 2).
Channels tried
Same Crossref micronutrient title search [12] (no trimethobenzamide record); Crossref anemia, hemolysis and methemoglobinemia title search [10] (no trimethobenzamide record). Repair pass: PubMed term listing "trimethobenzamide iron": 10 records, all ferroptosis, iron coordination chemistry or unrelated, none about trimethobenzamide [24]. A second Crossref phrasing returned HTTP 429. Label text [1][2][3]. The 114-record PubMed listing of the drug showed no iron, ferritin or anemia title in the pages read [21].
Gap type
Probable genuine gap, partly tooling-limited; not confirmed.
Gut Microbiome Risk
Each finding below is counted once, in this area only.
Gut microbiome risk
Not graded — disclosed evidence gapSee study details
No study of gut microbiome composition, diversity or function, and no in vitro growth-inhibition study of gut bacteria, with trimethobenzamide was found.
Full detail and limits
Gut microbiome risk
Not graded — disclosed evidence gapWhat the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded
Limits on what this shows
- Why no grade: Dual condition met: no Tier B or C evidence located and no circulating dysbiosis claim for trimethobenzamide located. Diarrhea is a labeled adverse reaction [1][2][3], but it is a clinical outcome listed without frequency or microbial data and is not microbiome evidence. A large in vitro screen of marketed drugs against gut strains exists in the wider literature, but whether trimethobenzamide was among the tested compounds could not be verified here (the paper and its drug-level supplement were not opened for this drug), so it supports no grade.
Channels tried
Crossref title search "trimethobenzamide microbiota bacteria growth inhibition": 15 records; six concerned trimethobenzamide (compendial and anesthesia titles), none paired it with microbiota or bacteria [11]. Repair pass, drug-microbiome screens first: (a) Maier 2018 Nature (Prestwick library, 1,197 drugs, 40 gut strains) article page opened via WebFetch: text does not name trimethobenzamide, and the supplementary drug table was not reachable (Springer supplementary file host disallowed by robots.txt; the PubMed Central copy PMC6108420 returned a bot check; Europe PMC full text disallowed and its API returned HTTP 429) [15][16]; (b) a reuse of the Maier data in a machine-learning paper (Pharmaceutics 2021) was opened and its supplementary Excel file S1 downloaded by the fetch tool as an unreadable binary, so the per-drug table could not be searched [17]; (c) Algavi and Borenstein 2023 (Nat Commun) and its bioRxiv preprint were opened: no trimethobenzamide in the extracted text [18][19]; (d) Nature 2025 medication-microbiome infection study opened: digoxin focus, no trimethobenzamide [20]; (e) a direct download of the Pharmaceutics supplement with curl returned HTTP 403 and was not pursued. PubMed term listings "trimethobenzamide microbiota" (6 records) and "trimethobenzamide bacteria" (10 records): all unrelated [26]. Label text [1][2][3]. Terms not reachable at abstract level: dysbiosis, 16S, fecal microbiota, C. difficile.
Gap type
Probable genuine gap with an unresolved tooling limit: whether trimethobenzamide was among the roughly 1,200 compounds tested by Maier et al. could not be established, because the drug-level supplementary table was never opened. If it was tested and inhibited a strain, that would be Tier B and a yellow grade. Re-check first, from a client that can open the Nature supplementary Excel files or the PubMed Central copy.
Oxygen and ATP Output
Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.
Oxygen delivery/utilization: outcome entry, labeled "blood dyscrasias" without frequency or type, not a nutrient deficiency
Yellow — LowEvidence: / outcome entry
The trimethobenzamide label lists "blood dyscrasias" among adverse reactions; no hemoglobin, hematocrit, red-cell, methemoglobin or oxygen-delivery measurement exists in a trimethobenzamide cohort in the sources opened.
Full detail and limits
Oxygen delivery/utilization: outcome entry, labeled "blood dyscrasias" without frequency or type, not a nutrient deficiency
Yellow — LowWhat the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow / outcome entry
Limits on what this shows
- Null / negative: No cohort or interventional study measuring hemoglobin, hematocrit or arterial oxygenation in trimethobenzamide users was found in the accessible channels; PubMed listings were blocked, so this is a probable, not confirmed, absence.
- At-risk subgroups: Not defined. Confounding by indication (vomiting, poor intake, febrile or infectious illness, surgery) is presumed (Hard Rule 6).
Regulatory status
Adverse reactions as extracted: "blood dyscrasias, blurring of vision, coma, convulsions, depression of mood, diarrhea, disorientation, dizziness, drowsiness, headache, jaundice, muscle cramps and opisthotonos" [1]; the capsule renderings list blood dyscrasias and jaundice among adverse reactions [2][3]. The extractions did not name anemia, hemolysis or methemoglobinemia, and stated that methemoglobin and hemolysis are not mentioned [1][2][3]. No frequency, onset or mechanism was given.
Population evidence
None for any hematologic or oxygen-delivery measure. A Crossref title search pairing trimethobenzamide with anemia, hemolytic anemia and methemoglobinemia returned 15 records, all other drugs or conditions (for example dapsone, phenazopyridine, rasburicase), none trimethobenzamide [10]. A web search for blood dyscrasia with trimethobenzamide surfaced a PubMed record on trimethoprim-sulfamethoxazole blood disorders, which was opened and excluded as a different drug [14].
Mechanism
Not stated. The label names no mechanism for the blood dyscrasias, and nothing in the sources opened ties them to a nutrient.
Counter-evidence held on record
Counter-evidence on record This is the drug's own labeled toxicity and a clinical outcome, not an oxygen-delivery deficiency and not iron, B12 or folate deficiency (Hard Rule 2). "Blood dyscrasias" is a nonspecific term, and the label gives no rate. It is graded yellow as a context flag only; the label is the single source, shared with the labeled-toxicity facts in the pharmacokinetic block (see the Overlap map). Framing caution Do not imply that any anemia on this drug is nutritional or that iron or other supplements are indicated. Unexplained fatigue, pallor, fever, sore throat or bruising during treatment warrants clinical review, including a blood count, by a prescriber.
ATP production
Not graded — disclosed evidence gapSee study details
No study of ATP content, ATP synthesis, oxidative phosphorylation or cellular energy output with trimethobenzamide was found.
Full detail and limits
ATP production
Not graded — disclosed evidence gapWhat the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded
Limits on what this shows
- Why no grade: Dual condition met: no Tier B or C evidence located and no circulating "low energy" or ATP claim for trimethobenzamide located. Drowsiness is a labeled effect of the drug's CNS pharmacology and is not an ATP deficiency. The label extractions contain no energy-metabolism statement [1][2][3].
Channels tried
Crossref title search with "respiration" and mitochondrial terms [9] (no trimethobenzamide record). Repair pass: Crossref "trimethobenzamide cellular ATP oxidative phosphorylation energy metabolism": 15 records, none naming trimethobenzamide [29]; PubMed term listing "trimethobenzamide ATP" returned HTTP 429 and was not read. Label text [1][2][3]. Terms not reachable at abstract level: membrane potential, lactate, phosphocreatine. The 1988 report that trimethobenzamide prevents aspirin-induced hypophagia (PMID 3147468, title only, not opened) concerns food intake, not ATP.
Gap type
Probable genuine gap, partly tooling-limited; not confirmed. Kept as its own entry per Hard Rule 7.
Claims checked and not supported
These circulate online for this medication. They are listed here only so they can be answered, never as findings, and they are not graded.
A claim with no supporting evidence is not necessarily disproven. Where evidence actually argues against a claim, that is stated below.
Any vitamin, mineral or physiological-category depletion attributed to trimethobenzamide
Where it comes from: None located. Seven WebSearch queries returned drug-information pages (Drugs.com, Mayo Clinic, MSK, medlibrary, DrugCentral) and unrelated titles; none of the pages reached asserted a depletion. The search budget was then exhausted, so the consumer-site audit was limited, not exhaustive.
Why it fails: No claim to rebut. This is not evidence that none circulates; a later revision should repeat the audit when search is available.
Vitamin B12, vitamin D3, calcium (listed as frequently checked on a consumer interaction page)
Where it comes from: Drugs.com interaction page for trimethobenzamide [7], which lists these among frequently checked items alongside a count of 245 drug interactions.
Why it fails: A lookup list, not a depletion claim; the page as summarized states no nutrient depletion and no mechanism. Tier D never supports a claim at any level. Nothing in the label [1][2][3] links the drug to these nutrients. Recorded so a reader who meets the listing knows it carries no finding.
How the body handles this medication
- Absorption
- Time to peak plasma concentration about 30 minutes after a 200 mg intramuscular dose. Oral absorption site, bioavailability and any named transporter were not in the label extractions opened.[1] [2] label text via WebFetch summaries
- Metabolism and enzymes
- One extraction states the primary metabolic pathway is oxidation forming trimethobenzamide N-oxide [2]; another label rendering states that metabolic disposition in humans is unknown and active metabolites are not characterized [3]. The two extractions disagree and the discrepancy was not resolved (both are summarizer outputs). No CYP450 enzyme is named in any extraction, and no induction or inhibition is stated, so absence of enzyme induction is "not documented", not "documented absent".[2] [3] [1]
- Elimination
- Mean elimination half-life 7 to 9 hours. Between 30 and 50 percent of a single dose is excreted unchanged in urine within 48 to 72 hours. A general reference page also lists fecal excretion; that was not found in the label extractions and is not relied on.[1] [3] label text; [6] reference page, not used
- Renal tubular handling and impairment
- No effect on renal tubular handling of water or electrolytes is described. A substantial route of elimination is renal and clearance in renal impairment is "not known"; dose adjustment is advised for creatinine clearance of 70 mL/min/1.73 m2 or less, and the label advises cautious dosing in the elderly with renal function monitoring.[1] [3]
- Food, mineral and antacid interactions
- None stated in any label extraction. The only labeled interaction is with alcohol (an "adverse drug interaction", magnitude not stated). A consumer interaction-checker page counts 245 drug interactions, 1 alcohol or food interaction and 3 disease interactions (Reye's syndrome, parkinsonism, renal impairment), and lists no nutrient depletion.[1] [2] [3] labels; [7] Tier D, context only
- Labeled toxicity (not nutrient findings)
- Hypersensitivity reactions and Parkinson-like symptoms; extrapyramidal symptoms, convulsions, opisthotonos and coma reported in the setting of acute febrile illness, gastroenteritis, dehydration and electrolyte imbalance; drowsiness; hypotension after parenteral use; blood dyscrasias, jaundice, muscle cramps, diarrhea, blurred vision and mood depression; concern about hepatotoxic effects in Reye's syndrome; injectable form contraindicated in pediatric patients. These are the drug's own toxicity under Hard Rule 2.[1] [2] [3] label text, Warnings and Adverse Reactions
- Mechanism and label provenance
- The label states the mechanism "may involve" the chemoreceptor trigger zone [1]. Dopamine D2 antagonism appears on a general reference page [6], which is not an evidence source here. Labels read: Par Health USA injection, set ID 7da90678-b229-4ad6-9193-2b8a3e9ba695, revision March 2026 per the extraction [1]; Direct_Rx capsule label, set ID 8ccb7a57-a1e4-55f7-e053-2a95a90a792b, via DrugCentral [2]; Drugs.com capsule prescribing information [3]. Read through summarizing fetch tools, not full-text downloads, on 2026-10-06.[1] [2] [3] [6]
What the research says is worth watching
General information from the medication label and the studies above. It is not personal medical advice, and any change belongs with your prescriber.
Labs
No routine nutrient labs indicated by this dossier
No red or orange finding exists. Testing should follow the underlying illness (prolonged vomiting or diarrhea, poor intake, surgery) and the prescriber's judgment, not trimethobenzamide alone.
Electrolytes and fluid
Illness-side monitoring, per the label
The label directs primary emphasis to restoring body fluids and electrolyte balance in gastroenteritis and febrile illness, where CNS reactions to the drug are more likely to be reported [1]. This is clinical management of the illness; dietary salt or supplements are not the remedy and none is recommended here.
Drug's own toxicity
CNS reactions, drowsiness, blood and liver signs
Extrapyramidal or Parkinson-like symptoms, convulsions, opisthotonos, drowsiness, hypotension after injection, jaundice and blood dyscrasias are labeled reactions [1][2][3]. The extractions gave no monitoring schedule. Unexplained pallor, fever, sore throat, bruising or yellowing of the skin or eyes should prompt prescriber review; this is drug toxicity, not a nutrient finding.
At-risk groups
Confounding by indication; renal impairment; elderly
People given an antiemetic often have vomiting, reduced intake or gastrointestinal illness, each of which lowers vitamins, minerals and electrolytes independently of the drug (Hard Rule 6). Reduced renal function (creatinine clearance of 70 or less) calls for dose adjustment, and the elderly warrant cautious dosing and renal monitoring [1].
Separation intervals
None required by the retrieved label text
No mineral, antacid, food or supplement separation interval is documented in the label extractions [1][2][3]. The only labeled interaction is alcohol, which is not a nutrient. No supplement-drug timing interaction is asserted.
Pregnancy, pediatric
Population notes
Pregnancy: rat and rabbit reproduction studies suggested no teratogenicity, but safety in pregnant and nursing women is not established [1]. Pediatric: the injectable form is contraindicated, and antiemetics are not recommended for uncomplicated vomiting in children per the capsule rendering [2]. No nutrient-specific pregnancy, renal or pediatric consideration arises because no nutrient entry is graded above yellow.
Overlap map, to prevent double counting
Electrolytes and fluid
Shares evidence with: Oxygen delivery/utilization; pharmacokinetic block
Note: Both yellow entries rest on the same regulatory text, read as three renderings [1][2][3] that are one label, not three independent sources. Their content (illness-electrolyte caution versus blood dyscrasias) is distinct.
Mitochondrial burden
Shares evidence with: Oxidative stress; ATP production
Note: All three are ungraded and rest on the same null search results [9] and label absence [1][2][3]. A repeated null is not independent confirmation of safety; kept separate per Hard Rule 7.
Copper
Shares evidence with: Iron; Oxygen delivery/utilization
Note: Same micronutrient and anemia null searches [10][12]. Independent entries.
Gut microbiome risk
Shares evidence with: None
Note: Rests on [11], the unopened Maier supplementary table [15][17] and the null reuse checks [18][19][20]; no shared primary source with other entries.
All entries
Shares evidence with: Search access limits
Note: Every ungraded card shares the same access limitation (rate-limited PubMed and Crossref, blocked Europe PMC, OpenAlex search and PubMed Central, exhausted WebSearch) and the same 114-record PubMed listing [21]. The six gaps are one tooling situation, not six independent confirmations.
All references used above
- TIGAN (trimethobenzamide hydrochloride) injection: FDA prescribing information (Par Health USA, LLC, DailyMed) — Regulatory label, Tier A. Set ID 7da90678-b229-4ad6-9193-2b8a3e9ba695; extraction reported label revision March 2026 and current version May 21, 2026. Read through a WebFetch summary, not a full-text download. Clinical pharmacology, indications, contraindications, warnings, precautions, adverse reactions and dosage read; no vitamin, mineral, electrolyte-depletion, iron, copper, methemoglobin, hemolysis, antacid or food statement.
- Trimethobenzamide capsule: FDA label rendering (Direct_Rx, repackager; DrugCentral label view) — Regulatory label text, Tier A (a mirror of the DailyMed set ID 8ccb7a57-a1e4-55f7-e053-2a95a90a792b). Read through a WebFetch summary. Source of the "trimethobenzamide N-oxide" metabolite statement; no vitamin, mineral, electrolyte, iron, copper, methemoglobin, hemolysis, antacid or food interaction named; alcohol interaction only.
- Trimethobenzamide capsules: prescribing information (Drugs.com Pro) — Label reproduction, read through a WebFetch summary. Reproduces half-life 7 to 9 hours, 30 to 50 percent unchanged in urine, renal dose caution and adverse-reaction list; the summary states metabolic disposition in humans is unknown, which conflicts with [2]. Not the primary DailyMed record.
- WHO Collaborating Centre for Drug Statistics Methodology: ATC/DDD Index, R06AA10 — Classification reference. Substance trimethobenzamide, group R06AA aminoalkyl ethers, within R06A antihistamines for systemic use. Read through a WebFetch summary.
- DailyMed search listing: trimethobenzamide — Used only to find label set IDs and to see the marketed forms (7 capsule and 5 injection records listed). Not an evidence source.
- Wikipedia: Trimethobenzamide — General reference, Tier D-equivalent. Used only for the brand name Tebamide and for the statement of D2 receptor antagonism and fecal excretion; supports no grade and no entry.Not a primary or peer-reviewed source; D2 and fecal-excretion statements are not confirmed in the label extractions.
- Drugs.com: trimethobenzamide drug interactions page — Consumer interaction checker, Tier D. Summary reported 245 drug interactions (5 major, 240 moderate), 1 alcohol or food interaction, 3 disease interactions, and vitamin B12, vitamin D3 and calcium among frequently checked items; no depletion claim. Read through a WebFetch summary.Tier D; supports no claim at any level.
- Crossref title search: trimethobenzamide — Listing of 40 titles shown (summarizer reported 61 records). Titles include 1960s clinical antiemetic trials, a 1967 hepatitis report, a 1976 neonatal extrapyramidal report, a 2004 elderly-patients item, a 1994 immunoassay cross-reaction item and a 2005 animal teratogenicity study. Titles only; none opened.
- Crossref title search: trimethobenzamide mitochondria oxidative stress respiration — 20 records, none naming trimethobenzamide. Read through a WebFetch summary.
- Crossref title search: trimethobenzamide hemolytic anemia methemoglobinemia — 15 records on dapsone, phenazopyridine, rasburicase and other drugs or conditions; none naming trimethobenzamide. A first, broader phrasing (adding "blood dyscrasia") returned HTTP 429 and was not read.
- Crossref title search: trimethobenzamide microbiota bacteria growth inhibition — 15 records; six were compendial or anesthesia titles on trimethobenzamide itself, the rest unrelated bacteria or nanomaterial papers; none paired trimethobenzamide with microbiota. A first phrasing (with dysbiosis and Clostridium) returned HTTP 429 and was not read.
- Crossref title search: trimethobenzamide iron copper zinc vitamin deficiency serum — 15 micronutrient records, none naming trimethobenzamide.
- Crossref title search: trimethobenzamide electrolyte sodium potassium serum — 15 electrolyte records, none naming trimethobenzamide. A first phrasing (with hyponatremia and hypokalemia) returned HTTP 429 and was not read.
- PubMed record 2266345 (surfaced by a web search for trimethobenzamide and blood dyscrasia) — Opened through a WebFetch summary: a Swedish report of blood disorders with trimethoprim-sulfamethoxazole, 1976 to 1985. Title, authors and journal were not in the retrieved text.Cohort excluded trimethobenzamide: the drug studied was trimethoprim-sulfamethoxazole. No finding is used.
- Maier L, Pruteanu M, Kuhn M, et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 2018;555:623-628 — In vitro screen of Prestwick library drugs (reported as more than 1,000, 1,197 in a reuse paper [17]) against 40 representative gut strains, in at least triplicate. Article page opened via a WebFetch summary on 2026-10-07: the text does not name trimethobenzamide. Supplementary Table 1 and the drug-level inhibition results were not reachable (see access note). DOI 10.1038/nature25979; PMID 29555994.Cohort membership of trimethobenzamide unverified; supplementary drug table not opened. Supports no grade.
- OpenAlex single-record lookup for DOI 10.1038/nature25979 — Metadata only (PMID 29555994, PMCID PMC6108420, journal and date). Used to locate the PubMed Central copy.Metadata record; not an evidence source. The PubMed Central copy returned a bot-verification page and could not be read.
- Machine Learning Uncovers Adverse Drug Effects on Intestinal Bacteria. Pharmaceutics 2021;13(7):1026 — Machine-learning reuse of the Maier 2018 data (1,197 drugs, 40 strains). Page opened via a WebFetch summary: trimethobenzamide is not named in the main text. The supplementary Excel file S1, said to hold all drugs and p-values, was fetched but returned as an unreadable binary file; a direct curl download was refused (HTTP 403) and not pursued. DOI 10.3390/pharmaceutics13071026.Per-drug table not opened; cohort membership of trimethobenzamide unverified. Supports no grade.
- Algavi YM, Borenstein E. A data-driven approach for predicting the impact of drugs on the human microbiome. Nat Commun 2023 — Computational prediction study that reuses the Maier 2018 screen. Opened via a WebFetch summary: trimethobenzamide is not named in the extracted text.Class-level reuse of other drugs; trimethobenzamide not shown in the cohort. Supports no grade.
- Preprint of the Algavi and Borenstein study (bioRxiv 10.1101/2022.10.08.510500) — Full-text page opened via a WebFetch summary on 2026-10-07: no mention of trimethobenzamide or antiemetics in the extracted text.Preprint; trimethobenzamide not shown in the cohort. Supports no grade.
- Medication-microbiome interactions that affect gut infection. Nature 2025 (article s41586-025-09273-8) — Population-cohort and mouse Salmonella study centered on digoxin. Opened via a WebFetch summary: no trimethobenzamide or antiemetic content.Trimethobenzamide not in the studied cohort as extracted. Supports no grade.
- PubMed listing: trimethobenzamide (114 records) — Pages 1 to 6 and 8 of 10-record listing pages read on 2026-10-07 through a WebFetch summary (titles only; page 7 returned HTTP 429, pages 9 to 12 not requested). Titles are clinical antiemetic trials (1959 to 1970), analytical chemistry, immunoassay cross-reaction, a 1967 hepatitis report, a 1976 neonatal extrapyramidal report, a 2011 neonatal rat toxicity study, apomorphine-pretreatment and gastroenteritis antiemetic reviews. None concerns mitochondria, redox, iron, copper, microbiome or energy metabolism by title. No record was opened.Titles only; none opened. Unread listing pages remain.
- PubMed term listing: trimethobenzamide mitochondria — 9 records, all unrelated (PubMed split the query into "tri" plus mitochondria); none about trimethobenzamide.
- PubMed term listing: trimethobenzamide oxidative stress — 10 records, all unrelated "tri-" chemical or oxidative-stress papers; none about trimethobenzamide.
- PubMed term listing: trimethobenzamide iron — 10 records (ferroptosis, iron coordination chemistry, aplastic anemia and others); none about trimethobenzamide.
- PubMed term listing: trimethobenzamide copper — 10 records of copper coordination chemistry or unrelated papers; none about trimethobenzamide.
- PubMed term listings: trimethobenzamide microbiota (6 records) and trimethobenzamide bacteria (10 records) — All records unrelated (immunology, NAFLD, biofilm and similar); none about trimethobenzamide. The bacteria query is the second URL.
- Crossref title search: trimethobenzamide mitochondrial membrane potential toxicity — 14 records; two named trimethobenzamide (USP compendial monographs for the drug and its injection, DOIs 10.31003/uspnf_m85860_05_01 and 10.31003/uspnf_m85880_03_01); the rest were unrelated membrane-potential papers and supplement files, including a computational in vitro mitochondrial toxicity paper (J Chem Inf Model 2018, supplement DOIs 10.1021/acs.jcim.8b00433.s001 and.s002) that was not opened. Titles only.Titles only; none opened.
- Crossref title search: trimethobenzamide glutathione reactive metabolite antiemetic — 15 records; eight named trimethobenzamide (1960 to 1967 clinical trials, a 2018 RP-UPLC assay, the 1988 aspirin hypophagia report, compendial monographs); the others were glutathione chemistry on other compounds. None concerned redox effects of trimethobenzamide. Titles only.Titles only; none opened.
- Crossref title search: trimethobenzamide cellular ATP oxidative phosphorylation energy metabolism — 15 records on ATP synthesis and oxidative phosphorylation; none naming trimethobenzamide.