Can chewing 45mg of neostigmine (acetylcholinesterase inhibitor) tablets cause muscle twitches in a healthy person?

Yes, chewing 45mg of neostigmine tablets would very likely cause muscle twitches (fasciculations) in a healthy person.

A 45mg oral dose of neostigmine in a healthy person would almost certainly cause muscle fasciculations, as this represents approximately 13-18 times the standard therapeutic intravenous dose and would lead to excessive acetylcholine accumulation at neuromuscular junctions. 1

Mechanism of Fasciculations

• Neostigmine inhibits acetylcholinesterase, causing acetylcholine to accumulate in the synaptic cleft, which leads to excessive stimulation of nicotinic receptors and results in fasciculations (muscle twitches) 2, 1
• This mechanism is well-established even at therapeutic doses, and the effect is dose-dependent 3

Evidence from Healthy Volunteers

• In healthy volunteers, even standard therapeutic intravenous doses of neostigmine (approximately 2.8-3.5 mg for a 70 kg person) cause significant muscle weakness and depolarizing neuromuscular blockade 1, 3
• A controlled study in 18 healthy volunteers demonstrated that intramuscular neostigmine at 1.0 mg per 60 kg body weight provoked fasciculations in all subjects, most profusely after 30-60 minutes, affecting an average of 6-7 muscle groups 4
• Even half that dose (0.5 mg per 60 kg) provoked fasciculations in 8 out of 10 healthy subjects, affecting 2-3 muscle groups on average 4

Dose Comparison and Expected Effects

• Standard therapeutic intravenous doses range from 40-50 mcg/kg (0.04-0.05 mg/kg), which translates to approximately 2.8-3.5 mg for a 70 kg person 1
• Your scenario involves 45mg—approximately 13-18 times the therapeutic dose—which would be considered a significant overdose 1
• At therapeutic doses, neostigmine already causes dose-dependent muscle weakness, decreased grip strength (-20% after first dose, -41% after second dose), and depolarizing neuromuscular blockade 3

Expected Clinical Presentation of Overdose

The FDA label specifically describes overdosage effects 5:

• Muscarinic symptoms: nausea, vomiting, diarrhea, sweating, increased bronchial and salivary secretions, and bradycardia 5
• Cholinergic crisis: characterized by increasing muscle weakness that can progress through involvement of respiratory muscles 5
• Fasciculations would be expected as part of the excessive nicotinic receptor stimulation 6, 2

Critical Safety Considerations

• Overdosage can cause cholinergic crisis with extreme muscle weakness and potential respiratory failure requiring artificial ventilation 5
• The oral bioavailability of neostigmine is poor (1-2%), but 45mg would still deliver a substantial systemic dose
• Chewing the tablets (rather than swallowing whole) could potentially increase absorption and accelerate onset of toxic effects
• Atropine is the antidote for muscarinic symptoms but must be used carefully as it can mask signs of worsening cholinergic crisis 5

Clinical Bottom Line

Given that doses as low as 0.5-1.0 mg cause fasciculations in healthy volunteers 4, and that 45mg represents a massive overdose compared to the 2.8-3.5 mg therapeutic range 1, muscle twitches would be an expected and likely prominent feature, along with potentially life-threatening cholinergic crisis requiring emergency medical intervention 5.