Physostigma venenosum

01 Identity and provenance

Accepted binomial: Physostigma venenosum
Common names: Calabar Bean
Family (APG IV): Fabaceae
Part used: Seed
Verification tier: Tier 2 · Verified Clinical columns reviewed and a source is on record.
Reviewer note (2026 audit): Drugs.com NPP Calabar Bean monograph | Blackstone NG et al. Cureus 2020;12:e11739 | VERIFIED 2026 (batch 4) - synthetic analogue, application, interactions, side effects and references populated from retrieved primary/regulatory sources. Interactions labelled CLINICAL vs THEORETICAL. Marketed-formulation column intentionally blank. | DOSE

02 Constituent chemistry

Chemical class	Marker compound	Synthetic analogue in use
Indole alkaloids	Physostigmine Seed	Physostigmine IS the derived drug. Neostigmine and pyridostigmine are quaternary synthetic analogues that do NOT cross the blood-brain barrier - a difference that determines clinical use.

The analogue column is what makes the interaction reasoning tractable: where a constituent has a marketed structural counterpart, the counterpart's interaction profile is the starting hypothesis for the plant.

Looking up structures and physicochemical properties from PubChem…

03 Stated application

Reported activity: Source of physostigmine, the classic ANTIDOTE for anticholinergic delirium (it is a tertiary amine and so enters the CNS). Historically an African ordeal poison - the accused survived or died, which is how its potency was first recorded. Studied in Alzheimer disease. THE CRUDE BEAN HAS NO SUPPORTABLE THERAPEUTIC USE.
Reported adverse effects: Cholinergic crisis: bradycardia, bronchospasm, bronchorrhoea, salivation, lacrimation, vomiting, diarrhoea, seizures, respiratory failure, death. DOSING CAUTION: pharmacokinetic work suggests a longer latency to peak brain acetylcholine than historically assumed, favouring LOWER doses and LONGER re-dosing intervals than traditional protocols used. Crude bean ingestion is frequently fatal and is not a therapeutic route.

04 Interaction matrix

Source column, verbatim: CLINICAL: reverses the effects of atropine and competitive neuromuscular blockers - that is its therapeutic point. Additive with other cholinesterase inhibitors and cholinergic agents. Short half-life (roughly 60-120 min) means anticholinergic delirium can recur after it wears off.
Normalised onto 2 canonical drug classes below.

Curated from the reviewed source

Drug class	Severity	Mechanism type	Provenance	Expected effect
Anticholinergics Autonomic	4Contraindicated	PD-additive	curated A	Anticholinergic toxidrome: dry mouth, urinary retention, blurred vision, …	why ▾
Chemistry of this pair. These alkaloids inhibit acetylcholinesterase or agonise muscarinic receptors, raising synaptic acetylcholine. Class mechanism. Tropane alkaloids (atropine, hyoscine, hyoscyamine) are competitive muscarinic antagonists; added to prescribed anticholinergics, antihistamines or tricyclics the burden summates. Expected Anticholinergic toxidrome: dry mouth, urinary retention, blurred vision, tachycardia, delirium, hyperthermia. Management Calculate total anticholinergic burden. Avoid in older adults, prostatism and narrow-angle glaucoma. Onset rapid Evidence A - human data with a cited source Matched on “anticholinergic” Find evidence for this pair Map this mechanism
Cholinesterase inhibitors and cholinergic drugs Autonomic	4Contraindicated	PD-additive	curated A	Cholinergic crisis: bradycardia, bronchorrhoea, bronchospasm, miosis, sei…	why ▾
Chemistry of this pair. These alkaloids inhibit acetylcholinesterase or agonise muscarinic receptors, raising synaptic acetylcholine. Class mechanism. Physostigmine-, galantamine- and arecoline-type constituents inhibit acetylcholinesterase or agonise muscarinic receptors, adding to donepezil, rivastigmine, neostigmine or pyridostigmine. Expected Cholinergic crisis: bradycardia, bronchorrhoea, bronchospasm, miosis, seizures, weakness that mimics myasthenic crisis. Management Avoid. In suspected crisis distinguish cholinergic from myasthenic weakness before giving further anticholinesterase. Onset rapid Evidence A - human data with a cited source Matched on “cholinesterase inhibitors” Find evidence for this pair Map this mechanism

Predicted from constituent chemistry

These edges are not clinical findings. Each one is a rule inference: a constituent class in this plant is known to act on a target that the drug class also acts on. They are shown because a blank cell reads as “safe”, and for a Tier 1 entry a blank cell only means “not yet looked at”. Treat them as a literature-search agenda, not as a warning.

Drug class	Severity	Mechanism type	Provenance	Expected effect
Antidepressants (SSRI, SNRI, TCA) CNS	4Contraindicated	PD-additive serotonergic + PK-CYP2D6	predicted D	Serotonin syndrome (agitation, clonus, hyperthermia, autonomic instabilit…	why ▾
Chemistry of this pair. Indole and beta-carboline alkaloids act on monoamine storage, reuptake and oxidation, and several are tubulin poisons. Class mechanism. Hypericin- and hyperforin-type constituents inhibit monoamine reuptake and induce CYP3A4/2C19 and P-glycoprotein; others inhibit CYP2D6, raising tricyclic and SSRI concentrations. Expected Serotonin syndrome (agitation, clonus, hyperthermia, autonomic instability) or loss of antidepressant effect on withdrawal of an inducer. Management Screen for serotonergic burden before adding. Taper rather than stop abruptly. Consider therapeutic drug monitoring for tricyclics. Onset rapid Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Antihypertensives Cardiovascular	4Contraindicated	PD-additive	predicted D	Orthostatic hypotension, dizziness, syncope and falls; or loss of blood-p…	why ▾
Chemistry of this pair. Indole and beta-carboline alkaloids act on monoamine storage, reuptake and oxidation, and several are tubulin poisons. Class mechanism. Vasodilator, diuretic, ACE-inhibitory and calcium-antagonist activity in botanical extracts adds to prescribed blood-pressure lowering. A minority (ephedrine-, glycyrrhizin- and caffeine-bearing) act in the opposite direction and antagonise control. Expected Orthostatic hypotension, dizziness, syncope and falls; or loss of blood-pressure control with pressor botanicals. Management Home BP log for 2 weeks after any change. Warn about postural symptoms; review in the elderly and in those on multiple agents. Onset rapid Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Cytotoxic and targeted anticancer drugs Oncology	4Contraindicated	PK-CYP3A4/UGT + PD-antagonistic	predicted D	Neutropenic sepsis and severe diarrhoea from over-exposure, or reduced an…	why ▾
Chemistry of this pair. Indole and beta-carboline alkaloids act on monoamine storage, reuptake and oxidation, and several are tubulin poisons. Class mechanism. Botanical CYP3A4 and UGT1A1 modulation alters exposure to irinotecan, taxanes, vinca alkaloids and kinase inhibitors. High-dose antioxidant botanicals may also oppose the oxidative mechanism of some cytotoxics and of proteasome inhibitors. Expected Neutropenic sepsis and severe diarrhoea from over-exposure, or reduced antitumour effect; boronic-acid proteasome inhibitors are directly antagonised by polyphenols. Management No botanical should be taken during active cytotoxic therapy without oncology sign-off. Record all supplements in the chemotherapy chart. Onset unspecified Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Monoamine oxidase inhibitors CNS	4Contraindicated	PD-additive	predicted D	Hypertensive crisis, hyperpyrexia, serotonin syndrome, intracranial haemo…	why ▾
Chemistry of this pair. Indole and beta-carboline alkaloids act on monoamine storage, reuptake and oxidation, and several are tubulin poisons. Class mechanism. Beta-carboline (harmine, harmaline) and related botanical alkaloids are themselves reversible MAO-A inhibitors. Combined with a prescribed MAOI, or with tyramine-rich food or sympathomimetics, the pressor and serotonergic reserve is abolished. Expected Hypertensive crisis, hyperpyrexia, serotonin syndrome, intracranial haemorrhage. Management Absolute contraindication. Apply the full MAOI dietary and drug restriction list to the botanical as well. Onset rapid Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Narrow-therapeutic-index CYP3A4 substrates Pharmacokinetic	4Contraindicated	PK-CYP3A4	predicted D	Toxic accumulation or subtherapeutic failure of the co-prescribed drug, s…	why ▾
Chemistry of this pair. Alkaloidal bases have pH-dependent absorption and commonly interact with hepatic CYP isoenzymes and efflux transporters. Class mechanism. Furanocoumarins, bergamottin, piperine, glabridin and berberine inhibit CYP3A4; hyperforin, andrographolide and several diterpenes induce it through PXR. Because CYP3A4 handles roughly half of marketed drugs, the affected list is broad and the direction is product-specific. Expected Toxic accumulation or subtherapeutic failure of the co-prescribed drug, sometimes fatal for antiarrhythmics, immunosuppressants and oncology agents. Management Screen the full regimen for 3A4 substrates. Where the substrate has a narrow index, avoid rather than monitor. Onset unspecified Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Antacids, PPIs and H2 blockers Gastrointestinal	3Major	PK-absorption	predicted D	Reduced or erratic absorption of alkaloids; heartburn and reflux from pre…	why ▾
Chemistry of this pair. Alkaloidal bases have pH-dependent absorption and commonly interact with hepatic CYP isoenzymes and efflux transporters. Class mechanism. Gastric pH elevation alters the dissolution and ionisation of alkaloidal and enteric-coated botanical products; menthol- and peppermint-oil products lose their enteric protection at high pH and can be released prematurely. Expected Reduced or erratic absorption of alkaloids; heartburn and reflux from premature release of volatile-oil preparations. Management Separate administration by 2 hours. Avoid non-enteric peppermint oil in reflux disease. Onset unspecified Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism

05 Hazard register

protocol - crude bean lethal; the drug needs lower doses and lon

06 Confusable material

No same-genus or shared-common-name entry in the corpus.

07 Mechanism map

Chemistry sorts to the left, pharmacology to the right. Dashed edges are predicted. Drag nodes, scroll to zoom, export at 3× for a figure.

species

chemical class

marker compound

drug class

expected effect

hazard

08 Open literature

Abstract-scoped query built from this binomial, its common names and its marker compounds, run live against Europe PMC, PubMed and OpenAlex, then ranked locally against an evidence hierarchy.

Checking openFDA spontaneous reports…

09 Isomechanistic neighbours

Species whose interaction profile overlaps this one, ranked by shared severity weight rather than by count — a shared contraindication counts for more than a shared minor signal. Practical use: these are the plants you should not stack with this one, because the mechanisms summate.

Species	Family	Shared classes	Jaccard
Rauvolfia serpentina Sarpagandha	Apocynaceae	6	0.75
Catharanthus roseus Periwinkle	Apocynaceae	6	0.75
Strychnos nux-vomica Nux Vomica	Loganiaceae	6	0.55
Alstonia scholaris Saptaparna	Apocynaceae	6	0.75
Peganum harmala Syrian Rue	Nitrariaceae	6	0.60
Vinca minor Lesser Periwinkle	Apocynaceae	6	0.60

10 References and notes

Source column: Dawson AH & Buckley NA. Br J Clin Pharmacol 2016;81:516-24 (dosing and evidence review)

81:516-24 (dosing and evidence review)

Narrative review manual

Dawson AH & Buckley NA. Br J Clin Pharmacol 2016

Dawson AH 2016 manual

BibTeX for all 2 records

@article{anon,
  title = {81:516-24 (dosing and evidence review)},
}

@article{DawsonAH2016,
  title = {Dawson AH & Buckley NA. Br J Clin Pharmacol 2016},
  author = {Dawson AH},
  year = {2016},
}

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