Overview of Scopolamine

Scopolamine, a tropane alkaloid and anticholinergic drug, is administered to manage nausea and vomiting associated with surgery recovery and motion sickness. Non-FDA uses of scopolamine include acting as a treatment option for chemotherapy nausea, gastrointestinal spasms, asthma attacks, depression, smoking cessation, and excessive sweating. Scopolamine acts as a powerful anti-nausea medication by competitively inhibiting the muscarinic acetylcholine/M1 receptor in the medulla oblongata (the brain area that governs vomiting). By competing with acetylcholine at this receptor, peripheral anti-muscarinic properties and central sedative, anti-emetic, and amnestic effects are observed in patients.

Scopolamine is usually administered via a transdermal patch with onset of effect at 4 hours and peak impact at 24 hours. The potential adverse effects of scopolamine – agitation, confusion, psychosis (hallucinations, paranoia, and delusions) – allude to biochemical features of acetylcholine and its receptors. This information opens possibilities to study neurodegenerative brain diseases.¹

Scopolamine is a powerful muscarinic M1 antagonist which induces cholinergic-induced cognitive deficits which researchers can study in a controlled manner. The dosage of scopolamine affects the type of cognitive disruption observed. At lower doses, scopolamine affects attention; higher doses impact memory, learning and movement. Injections of scopolamine into the cerebrum impact anxiety, taste, and short-term memory. To study age- and dementia-related diseases, scopolamine has been used in neuropsychopharmacology to induce disease in animal models. Scopolamine-induced memory loss or cholinergic amnesia can model dementia because the disease is similarly characterized by a decline in cognitive functions caused by a decrease in the integrity of cholinergic neurotransmission.

However, clinical trials following this direction have led to disappointing results; a drug that can reverse scopolamine-induced memory loss might not have the potential to treat dementia. This constraint is a limitation in using scopolamine-induced memory loss to model age-related cognitive decline. More focus has been on using scopolamine to understand acetylcholine’s role in cognitive integrity. The findings indicate that acetylcholine is primarily involved in attentional processes and neural plasticity, and not as much learning and memory processes.² 

Another study found that gomisin A can reverse scopolamine-induced cognitive impairments because it enhances the cholinergic nervous system when it inhibits the activity of acetylcholinesterase. To successfully treat dementia, Alzheimer’s disease and some other age-related cognitive impairments, restoring cholinergic function is critical. Prolonging of the availability of acetylcholine by inhibiting acetylcholinesterase activity is one means of restoring cholinergic activity. Gomisin A has been shown to achieve this in animal models only. Although Kim et al. conclude that gomisin A is a hopeful drug prospect due to its anti-amnestic properties, it is important to remember that animal models and human drug development are still different fields. ³

The muscarinic cholinergic receptor system is expansive and thus lends scopolamine huge research potential in neuropsychopharmacology. The off-label uses of scopolamine, particularly depression, are associated with scopolamine’s ability to interact with the M1 receptor network in varied capacities. Hyperactivity in the muscarinic cholinergic receptor system has been linked to depression. Drevets et al. write that scopolamine delivered at 4.0 mg/kg intravenously produced a robust antidepressant effect, which is very promising. Reserchers further claimed to have found an effective dose which would prevent scopolamine-induced delirium and cognitive impairment. Women were found to have a more positive response to scopolamine for depression than men.⁴

References

1. Riad M, Hithe CC. Scopolamine. [Updated 2023 May 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554397/
2. Inge Klinkenberg, Arjan Blokland The validity of scopolamine as a pharmacological model for cognitive impairment: A review of animal behavioral studies, Neuroscience & Biobehavioral Reviews, Volume 34, Issue 8, 2010, Pages 1307-1350, ISSN 0149-7634, https://doi.org/10.1016/j.neubiorev.2010.04.001.(https://www.sciencedirect.com/science/article/pii/S0149763410000837)
3. Kim DH, Hung TM, Bae KH, Jung JW, Lee S, Yoon BH, Cheong JH, Ko KH, Ryu JH. Gomisin A improves scopolamine-induced memory impairment in mice. Eur J Pharmacol. 2006 Aug 7;542(1-3):129-35. doi: 10.1016/j.ejphar.2006.06.015. Epub 2006 Jun 15. PMID: 16824513.
4. Wayne C. Drevets, Carlos A. Zarate, Maura L. Furey, Antidepressant Effects of the Muscarinic Cholinergic Receptor Antagonist Scopolamine: A Review, Biological Psychiatry, Volume 73, Issue 12, 2013, Pages 1156-1163, ISSN 0006-3223, https://doi.org/10.1016/j.biopsych.2012.09.031.(https://www.sciencedirect.com/science/article/pii/S0006322312008918)