Potential Use of Nicotinic Receptor Agonists for the Treatment of Chemotherapy-Induced Cognitive Deficits

Abstract

Over the past several decades, research in both humans and animals has established the existence of persistent cognitive deficits resulting from exposure to chemotherapeutic agents. Nevertheless, there has been very little research addressing the treatment of chemotherapy-induced cognitive deficits and there is currently no approved treatment for this condition, often referred to as 'chemo-brain.' Several drugs that enhance cholinergic function and/or increase nicotinic acetylcholine receptor (nAChR) activity have been demonstrated to improve cognitive performance and/or reverse cognitive deficits in animals, findings that have led to the use of these compounds to treat the cognitive deficits present in a variety of disorders including attention deficit disorder, Alzheimer's disease, Parkinson's disease and schizophrenia. Although nAChR agonists have not been assessed for their efficacy in treating chemotherapy-induced cognitive deficits, these drugs have been shown to produce measureable increases in performance on several behavioral tasks known to be disrupted by exposure to chemotherapeutic agents. While the processes underlying chemotherapy-induced cognitive deficits may differ from those underlying other disorders, there appears to be a broad spectrum of application for the use of nAChR agonists to improve cognitive function. Therefore, studies examining the use of these drugs in the treatment of chemotherapy-induced cognitive deficits should be conducted as they may be of benefit for the treatment of 'chemo-brain.'

Insights Into Nicotinic Receptor Signaling in Nicotine Addiction: Implications for Prevention and Treatment

“…It has been suggested that receptor desensitization is a major contributor to the upregulation of nAChR subunits that is observed in chronic users of nicotine-containing products [ 154 , 157 ]. Because of the relatively conserved receptor binding sites of nAChRs for conventional agonists such as acetylcholine, [ 143 ] the subtype selectivity of allosteric modulators may be achieved easily by designing drug ligands that bind to various allosteric sites in diverse nAChR subunits [ 116 , 123 , 124 , 158 - 165 ].…”

Acute Effects of Nicotine on Physiological Responses and Sport Performance in Healthy Baseball Players

“…A meta-analysis study determined nicotine to have significant positive effects on six domains: fine motor control, alerting attention, orienting attention, short-term episodic memory, and working memory [ 39 ]. Furthermore, nicotine was reported to relieve certain attentional and cognitive deficits associated with Alzheimer’s disease, clinical symptoms of attention-deficient hyperactivity disorder, and clinical symptoms of Parkinson’s disease [ 40 ]. A systemic review demonstrated positive evidence on the effects of nicotine on attention and fine motor control in smokers, and the corresponding meta-analysis revealed a relatively small effect size (d = 0.13–0.34) for alerting and orienting attention in the smokers compared with healthy non-smokers [ 39 ].…”

Natural Compounds Interacting with Nicotinic Acetylcholine Receptors: From Low-Molecular Weight Ones to Peptides and Proteins

“…All compounds, for which we revealed interactions with the muscle-type and α7 nAChRs, acted as antagonists. Finding agonists, especially selective ones, might be even more interesting, because activation of neuronal nAChRs at certain conditions can be considered as a way of treating neurological pathologies [ 32 ]. For example, α7 nAChR activator EVP-6124 shows positive results in clinical trials of treating conditions such as schizophrenia [ 33 ]; ABT-594 is a less toxic epibatidine analog with analgesic properties [ 34 ].…”