What is the Difference Between Neostigmine and Physostigmine?

Neostigmine and physostigmine are both carbamates and reversible inhibitors of acetylcholinesterase, the enzyme that degrades acetylcholine. They increase concentrations of acetylcholine, causing stimulation of both muscarinic and nicotinic receptors. However, there are some differences between the two:

1. Structure: Neostigmine is a quaternary ammonium compound, while physostigmine is a tertiary amine. This difference in structure affects their ability to penetrate the blood-brain barrier (BBB). Physostigmine can penetrate the BBB, while neostigmine cannot.
2. Effect on neuromuscular transmission: Both neostigmine and physostigmine increase the amplitudes of miniature endplate potentials (MEPP) in a dose-dependent manner. However, physostigmine also decreases the quantal content, which is related to the amount of transmitter released upon nerve stimulation, while neostigmine does not alter quantal content.
3. Onset and duration: Neostigmine has a slower onset of 7–11 minutes and a longer duration of effect of 60–120 minutes. In contrast, physostigmine has an onset of action within 3–8 minutes and a duration of effect of usually 30–90 minutes.
4. Indications: Neostigmine is used for the management of severe anticholinergic syndrome, such as agitated urinary retention, severe sinus tachycardia, or hyperthermia with absent sweating. Physostigmine is used to reverse neuromuscular blocking and has nonspecific analeptic (arousal) effects due to cholinergic stimulation of the reticular activating system of the brainstem.
5. Side effects: Both neostigmine and physostigmine have side effects, including cholinergic syndrome, nausea, vomiting, diarrhea, anorexia, and dizziness.

Comparative Table: Neostigmine vs Physostigmine

Neostigmine and physostigmine are both carbamates and reversible inhibitors of acetylcholinesterase, the enzyme that degrades acetylcholine. They increase concentrations of acetylcholine, causing stimulation of both muscarinic and nicotinic receptors. However, there are some differences between the two medications:

Neostigmine is primarily used to treat myasthenia gravis, Ogilvie syndrome, and urinary retention without the presence of a blockage. It is administered through intramuscular (IM) or intravenous (IV) methods, subcutaneous injection, or orally. The effects arise after about 30 minutes from the time of administration and may last up to 4 hours.

Physostigmine, on the other hand, is used for the management of severe anticholinergic syndrome, including agitated urinary retention, severe sinus tachycardia, or hyperthermia with absent sweating, from antimuscarinic agents such as benztropine, atropine, jimson weed (Datura), and diphenhydramine. It has nonspecific analeptic (arousal) effects due to cholinergic stimulation of the reticular activating system of the brainstem.