Galantamine, a reversible inhibitor of acetylcholinesterase, exhibits both acetylcholinesterase-inhibiting and neuroprotective properties. The FDA (Food and Drug Administration) and EMA ( European Medicines Agency) have approved it for use in the treatment of Alzheimer's disease dementia (AD). The side effects associated with oral administration include gastrointestinal irritation, first-pass hepatic metabolism leading to reduced bioavailability and systemic adverse reactions such as nausea or liver enzyme elevation. These issues have led to the exploration of alternative delivery routes, such as transdermal, intranasal, or buccal. Such routes can bypass the gastrointestinal tract and liver, thereby reducing the risk of digestive discomfort and hepatic strain. The FDA has approved acetylcholinesterase inhibitors, such as rivastigmine, for transdermal administration in the form of patches. Studies on the transdermal administration of galantamine are ongoing. In addition to its use for AD, galantamine is increasingly being investigated for its effects on various conditions, including its potential in treating peripheral nervous system damage. In Bulgaria, a method for depositing galantamine through iontophoresis has been developed and widely used in clinical practice for many years. However, there is a lack of scientific evidence to support its effectiveness according to modern scientific approaches, necessitating further research in this direction.

Peripheral nerve injuries can lead to significant functional impairments, and treatment options remain limited. Galantamine, widely used for cognitive disorders, has shown potential effects on the peripheral nervous system, making it a candidate for new therapeutic approaches. The narrative review explores the use of galantamine for peripheral nerve injuries, with a focus on transdermal and iontophoretic delivery methods. Searches in scientific databases revealed no peer-reviewed publications addressing this specific application. As a result, the review expanded to include printed and offline sources and a broader timeframe to capture earlier reports. Available evidence from Bulgaria suggests that galantamine ampules have been applied via iontophoresis for peripheral neuropathy. However, this approach is not documented in established scientific databases, and information on its safety and effectiveness is limited. Overall, research on transdermal galantamine for peripheral nerve injuries is still scarce. More studies are needed to better understand its potential benefits and to optimize safe delivery methods.

Background: Peripheral neuropathy is a common and clinically heterogeneous neurological condition caused by metabolic, inflammatory, toxic, or traumatic factors and is associated with sensory deficits, neuropathic pain, motor impairment, and reduced functional capacity. Management remains challenging and often requires multimodal therapeutic approaches, as pharmacological monotherapy frequently provides incomplete symptom control. Objective: This narrative review explores the conceptual rationale for combining galantamine with iontophoresis and Black Sea brine-based therapy as a potential multimodal strategy for peripheral neuropathy management. Main Findings: Galantamine, a reversible acetylcholinesterase inhibitor and positive allosteric modulator of nicotinic acetylcholine receptors, has demonstrated neuroprotective, neuromodulatory, and anti-inflammatory properties in experimental settings. Iontophoresis may provide a non-invasive method for targeted local drug delivery while reducing systemic exposure. Black Sea brine, widely used in Bulgarian balneological and rehabilitation practice, has been associated with improved circulation, pain reduction, and neuromuscular support. The reviewed evidence suggests biologically plausible complementary mechanisms; however, no direct clinical studies evaluating the combined intervention were identified. Limitations: Current evidence is indirect and derived from separate investigations of galantamine, iontophoresis, and brine-based therapy, as well as heterogeneous historical and regional sources. Therefore, the proposed combination should be considered hypothesis-generating rather than evidence-established. Conclusions: The combination of galantamine, iontophoresis, and Black Sea brine represents a potentially interesting multimodal concept for peripheral neuropathy rehabilitation. Well-designed preclinical and clinical studies are required to determine safety, feasibility, optimal treatment parameters, and therapeutic efficacy.