Christina Nault is a 2024 PharmD candidate at the University of Connecticut.

Christina Nault 

Patients who develop neurologic disorders require a complicated array of medications. The common culprit leading to these diseases is the worsening condition of certain neurotransmitter systems and malfunctioning neural networks.

Researchers from universities around the Middle East have completed a review article to examine small molecules to treat Alzheimer disease (AD). They specifically looked at the acetylcholinesterase inhibitor tacrine.

Tacrine was originally brought to the market in 1993 as an acetylcholinesterase inhibitor to fight the symptoms of AD, although manufacturers would withdraw it in 2013 due to hepatic toxicities. Acetylcholinesterase inhibitors have cholinergic actions but can modulate muscarinic and nicotinic receptors.

Ongoing research indicates that tacrine targets a wider array of pathways than previously believed, opening the doors for investigators to explore potential benefits of the drug for other conditions.

Research reveals some novel uses for tacrine—for example, it seems to mitigate ketamine’s adverse effects. It may also address delirium and psychological disturbances during the period immediately after administering anesthesia.

An interesting finding is the use of a hybrid of tacrine and melatonin, using the rationale that melatonin’s ability to neutralize free radicals would be advantageous. In people with neurological disorders, tacrine significantly increases cerebral blood flow, a significant discovery for stopping future neurologic diseases.

An additional area of great interest is pairing nitric oxide with tacrine analogs to increase blood flow and decrease inflammatory responses. The increase of blood flow to the brain is essential for neurologic diseases.

Investigators all over the world are looking for tacrine derivatives as possible future treatment options. Different researchers have looked at its structure and made substitutions on its ring, bound it to other compounds to reduce toxicity, and made similar molecular alterations to improve safety, tolerability, and efficacy.

Some of these compounds modulate neurogenesis; some modulate neuroinflammation; and some modulate endoplasmic stress, apoptosis (programmed cell death), energy metabolism, and calcium homeostasis. These findings could be groundbreaking in the quest to treat many different diseases.

These findings could mean major progress in the fight to mitigate or cure AD and possibly many other diseases with no cure. The discovery of linking tacrine to a ligand may improve its risk benefit profile and may lead to tremendous therapeutic potential.

The newer versions of tacrine are in preclinical trials, not human trials, but it is moving in the right direction. On top of reconsidering tacrine for the treatment of AD, researchers have used tacrine as a tool to induce Parkinson disease in animals to then test other drugs for efficacy. All of this means that tacrine-like drugs may hopefully someday make their way to the market and change many lives.

Christina Nault is a 2025 PharmD candidate at the University of Connecticut.

Mitra S, Muni M, Shawon NJ, et al. Tacrine Derivatives in Neurological Disorders: Focus on Molecular Mechanisms and Neurotherapeutic Potential. 

. 2022;2022:7252882. Published 2022 Aug 18. doi:10.1155/2022/7252882

Articles

Tacrine was originally brought to the market in 1993 as an acetylcholinesterase inhibitor to fight the symptoms of Alzheimer disease.

Reexamining the Use of Tacrine for Neurological Diseases

When people think about Parkinson disease (PD), it typically involves tremors, rigid movements, and akinesia. However, a large amount of people who are diagnosed with PD also experience sleeping disorders, which many say is the worst symptom of all. The most common disorders are insomnia, sleep disordered breathing (SDB), excessive daytime sleepiness (EDS), REM sleep behavior disorder (RBD), and restless leg syndrome (RLS).

Although the treatment of motor symptoms is important, more focus should be put on helping patients with PD with their sleep disorders because it means a better quality of life. This is where pharmacists can step in and help patients with PD.

Researchers from Germany recognized a need for a deeper dive into the non-motor symptoms (NMS) of PD because of the negative impact on quality of life. They did this by searching through PubMed for controlled clinical trials involving PD in relation to sleep disorders.

The place to start in the quest to decrease NMS effecting patients’ quality of life is to gather an extensive health history, focusing on sleep interruptions throughout the night. However, when choosing treatment options, it is also important to obtain information about other conditions that may be causing sleep disorders. Clinicians need to consider both objective and subjective measures to see the whole picture.

After information collection is complete, clinicians can work with patients to consider pharmacologic and non-pharmacologic therapies. One of the most important counseling points for health care workers to share with patients and their caregivers pertains to sleep hygiene with some simple tips and tricks to set patients up for a successful night of sleep.

Below is a chart on specific sleep conditions and their recommended treatment options.

PD is associated with many complications that can severely inhibit patients’ day-to-day lives. Sleep disorders are one of these complications and researchers are taking a closer look at ways to improve care.

Greater acknowledgement of sleep disorders has led to an influx of trials to find the best approach. As more time and effort are spent on this topic, patients will begin to see a more personalized approach to their therapy regimen.

Schütz L, Sixel-Döring F, Hermann W. Management of Sleep Disturbances in Parkinson's Disease [published online ahead of print, 2022 Jul 30]. 

. 2022;10.3233/JPD-212749. doi:10.3233/JPD-212749

Although the treatment of motor symptoms is the primary focus of care for Parkinson disease, helping these patients with sleep disorders is vital because of the impact on quality of life.

Parkinson Disease is More Than Just a Movement Disorder

Neurodegenerative diseases—such as Alzheimer disease, Parkinson disease, and Huntington disease—affect millions of people worldwide and the quest to find effective treatments is ongoing. These disorders are often caused by mitochondrial malfunction and the reactive oxygen species (ROS) that are subsequently produced.

Neurotoxicity and cell death can also be caused by excitotoxicity, synaptic dysfunction, impaired protein degradation systems, endoplasmic reticulum stress, DNA damage, inflammation, and cell cycle reentry. The long list of possible causes is why it is so difficult for researchers to find a cure for these progressive diseases.

However, many researchers are taking their strategies in a new direction by looking into antioxidant treatment as a possible intervention. One of the major concerns with neurodegenerative diseases is the substantial increase in ROS. Researchers are hopeful that by introducing antioxidant molecules, the oxidative equilibrium will be reset.

Researchers from Spain and the United Kingdom recently published a review of current efforts in this area in the 

International Journal of Molecular Sciences

. In it, they review mechanisms and drugs of most interest.

Because the brain is highly vulnerable to oxidative stress, decreasing the amount of ROS being produced could be critical. Antioxidants are capable of converting highly destructive free radicals and nonradical molecules, thereby reducing cerebral stress. These antioxidants can be enzymatic, non-enzymatic, endogenous, and exogenous. Although they do not all work in the same mechanisms, they all work to defend the brain from degeneration.

The most common types of agents involved in testing around the world include exogenous antioxidants, which include polyphenols, carotenes, and vitamins. However, researchers are taking a closer look at different hormones, such as melatonin, because of their neuroprotective properties. The latest randomized trial included antioxidants such as resveratrol, carotenoids, omega-3 fatty acids, vitamin E, and melatonin in patients with Alzheimer disease.

Each of these different substances have various effects on their potential improvement of neurodegenerative diseases. Resveratrol has antioxidant, anti-inflammatory, and neuroprotective abilities and when combined with donepezil, can help increase patients’ inflammatory response.

Carotenoids in combination with omega-3 fatty acid and vitamin E have seemed to improve active memory in older patients. Melatonin is the newest addition to clinical trials and researchers are hopeful it will help patients with Alzheimer disease with non-rapid eye movement sleep.

The researchers have faced many limitations while searching for a possible drug contender due to the fact that the clinical trials failed. Many show reports of the antioxidant treatment having no serious improvements in the patients’ symptoms. Environmental factors such as exercise and diet could also play a role in these unpromising results.

Researchers all over the world are taking part in the quest to find treatment options for neurodegeneration diseases, including Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic later sclerosis, and traumatic brain injury. Many of them are diving into the world of using antioxidant agents, one of the most being melatonin. The use of melatonin and other related antioxidant treatments is still in its early phases but could hold a promising future for neurogenerative disease.

Christina Nault is a 2025 PharmD candidate at the University of Connecticut

Morén C, deSouza RM, Giraldo DM, Uff C. Antioxidant Therapeutic Strategies in Neurodegenerative Diseases. 

. 2022;23(16):9328. Published 2022 Aug 19. doi:10.3390/ijms23169328

Antioxidants are capable of converting highly destructive free radicals and nonradical molecules, thereby reducing cerebral stress.

Antioxidants: A New Therapy for Neurodegenerative Diseases?

About 3.4 million people nationwide have active epilepsy and pharmacists can ensure that epilepsy does not control their lives. Globally, an estimated 65 million people suffer from epilepsy, which causes recurring, unprovoked seizures, and is the world’s fourth most common neurological disorder.Epilepsy comes with its own series of comorbidities, such as learning disabilities, autism, anxiety, and depression.

The goal of treatment for epilepsy is to help patients lower their seizure rate to zero with minimal adverse events (AEs). Many patients with epilepsy continue to experience uncontrolled seizures despite taking multiple antiseizure medications. Despite the 

ability of more than 20 FDA-approved antiepileptic drugs

 for the treatment of epilepsy, treatment outcomes have remained relatively stagnant for the past 20 years.

diagnosed following 2 unprovoked seizures

 or 1 unprovoked seizure with the likelihood of more that are not caused by a known and reversible medical condition. Most epilepsy cases manifest during childhood and frequently evolve in later years.

Many patients with epilepsy will experience multiple types of seizure along with symptoms of other neurological conditions. The disease is also common among individuals 55 years of age and older, with close to 1 million US adults in this age group diagnosed with the condition.

The William S. Middleton Memorial Veterans Hospital (WSMVH) in Madison, Wisconsin offers an epilepsy clinic each year to provide care for veterans. The multidisciplinary team involves the help of clinical pharmacy practitioners (CPP) and pharmacy residents who guide patients in understanding their medication regimen and the importance of medication adherence. 

Although this clinic has been around for decades, the current group of health care workers sought to perform a study on the impact of pharmacists on patient outcomes.

WSMVH created a single-center, retrospective, quality improvement project to evaluate pharmacists’ impact on the epilepsy clinic. Between October 2017 and June 2021, they performed a chart review of 446 patients seen by CPPs or pharmacy residents to assess the different types of interventions that occurred during the visits.

Some of the treatment interventions included:

Nonpharmacologic interventions (including education)

Consultations to other specialties placed

Early screening, detection, and treatment of comorbidities are essential in the care of epilepsy patients. Pharmacists have been a part of many treatment interventions throughout the years at the WSMVH epilepsy clinic, handling 43% of patients who came through the clinic. Overall, the addition of pharmacists to the health care team allowed more timely access to care for the patients.

Patients with epilepsy rely on medications to help them maintain a sense of normalcy in their daily lives. Pharmacists support these patients, as exemplified through this study. Epilepsy is a complicated disease that requires time and attention, and patients deserve the top level of care. Pharmacists are an essential cog in the machination that is epilepsy.

Taube M, Kotloski R, Karasov A, Jones JC, Gidal B. Impact of Clinical Pharmacists on Access to Care in an Epilepsy Clinic.

2022;39(Suppl 1):S5-S9. doi:10.12788/fp.0252

Pharmacists are an essential part of improving care for patients with epilepsy.

The Impact of a Pharmacist on Epilepsy

Pharmacists are accessible and caring health care providers who should be aware of how they can help patients with Parkinson disease (PD). Patients with PD should have access to any and all resources that help them live as comfortably as possible. Managing their pain is a crucial part of comfort.

A research group from the Department of Neurology at Jena University Hospital in Jena, Germany performed a cross sectional cohort study in hopes of creating a multidimensional approach for pain management for PD patients. During their study, they found that PD patients’ pain is often underdiagnosed and undertreated.

This is where pharmacists can step in and use their knowledge to improve health-related quality of life.

The researchers conducted this cross-sectional cohort study in an inpatient setting at Jena University Hospital. They enrolled 52 patients with PD who did not also have dementia and assessed them at the beginning of their hospital stay.

Motor function, nonmotor function, health-related quality of life and the Coping Strategies Questionnaire were assessed. They used the multivariate analysis of variance (MANOVA) to investigate the association between coping, clinical parameters, and quality of life.

From the results of the assessments, researchers were able to conclude that the coping strategies of the 52 participants could be grouped into active (handle pain using internal resources to control the pain) or passive (praying/hoping) coping strategies.

They found that patients who used active coping strategies had better physical functioning and more energy, whereas passive coping strategies had the opposite effect. The study revealed that pain was mostly associated with female sex, higher motor impairment, depression, and passive coping strategies.

All studies, have limitations. This study was largely centered around how participants managed their pain and how it affected their health-related quality of life, so it is important to acknowledge different variables. Quality of life can be influenced by both external (finances, social contacts, treatment, etc) and internal (personality traits) factors.

This could sway some findings, and participants may have factors other than their PD affecting their quality of life outside of pain.

Untreated pain can lead to depression, low self-esteem, frustration, and sleep deprivation. However, with the help of pharmacists and a team of health care providers, a better quality of life is possible for these patients.

Pharmacists can check in with their patients while they are at the pharmacy picking up their medications. It does not require any additional appointments and patients will see that pharmacists are there for them.

Becoming familiar with both pharmacologic (pain medications) and nonpharmacologic (physiotherapy, occupational therapy, behavioral therapy, cognitive behavioral therapy, stress management, relaxation training) pain coping strategies will benefit everyone.

1. Prell T, Liebermann JD, Mendorf S, Lehmann T, Zipprich HM. Pain coping strategies and their association with quality of life in people with Parkinson's disease: A cross-sectional study. 

. 2021;16(11):e0257966. Published 2021 Nov 1. doi:10.1371/journal.pone.0257966

With the help of pharmacists and a team of health care providers, a better quality of life is possible for patients with Parkinson disease.

Active or Passive Coping? A Study on Coping Strategies for Patients with Parkinson Disease

The FDA has officially accepted the investigational drug, 

 for review. Deucravacitinib is designed to work as a tyrosine kinase 2 (TYK2) inhibitor for the treatment of patients with moderate to severe 

Deucravacitinib will be the first TYK2 inhibitor approved for treatment of disease. Currently, deucravacitinib is in the midst of the POETYK PSO-2 trials.

Patients participating in these trials have achieved a Psoriasis Area and Severity Index (PASI 75), which means that after 16 weeks of treatment, they have at least 75% improvement in symptoms.

The researchers have also observed a static Physician’s Global Assessment (sPGA) score of clear or almost clear. When deucravacitinib was compared to apremilast, 58.7% and 53.6% of patients achieved PASI 75 throughout the 2 trials compared to apremilast, with which 35.1% and 40.2% of patients achieved the same, respectively.

Deucravacitinib increased and maintained its efficacy at the 6-month and 1-year check-in. Overall, this drug will be a possible solution for patients with psoriasis who wish to have the convenience of an oral medication.

TYK2 is an intracellular kinase involved in signaling of the cytokines that lead to plaque psoriasis. Deucravacitinib selectively inhibits TYK2 via allosteric mechanism inhibiting interleukin (IL)-12, IL-23, and type 1 interferon (IFN) pathways.

 Deucravacitinib binds to the nonconserved regulatory domain of the kinase effectively antagonizing TYK2.

Deucravacitinib’s proposed dosing is 3 mg twice daily, 6 mg twice daily, 12 mg once daily by mouth (in trial stages).

The most common AEs include headache, nasopharyngitis, rash, and sinusitis.

Researchers suggest that this TYK2 Inhibitor appears to be a safer alternative to JAK class of medications.

Deucravacitinib has not yet been tested in pregnant or breastfeeding individuals.

POS0198 EFFICACY AND SAFETY OF DEUCRAVACITINIB, AN ORAL, SELECTIVE TYROSINE KINASE 2 INHIBITOR, IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS: RESULTS FROM A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL. BMJ Journals. Accessed March 7, 2022. https://ard.bmj.com/content/80/Suppl_1/314.2

Bristol Myers Squibb Announces Positive Topline Results from Second Pivotal Phase 3 Psoriasis Study Showing Superiority of Deucravacitinib Compared to Placebo and Otezla. Bristol Myers Squibb. February 2, 2021. Accessed March 7, 2022. 

https://news.bms.com/news/details/2021/Bristol-Myers-Squibb-Announces-Positive-Topline-Results-from-Second-Pivotal-Phase-3-Psoriasis-Study-Showing-Superiority-of-Deucravacitinib-Compared-to-Placebo-and-Otezla-apremilast/default.aspx

Bristol Myers’ next-gen immunology med busts Amgen’s Otezla in head-to-head study. April 23, 2021. Accessed March 7, 2022. https://endpts.com/bristol-myers-next-gen-immunology-med-busts-amgens-otezla-in-head-to-head-study-is-a-showdown-coming/

Deucravacitinib in Moderate to Severe Psoriasis: Clinical and Quality-of-Life Outcomes in a Phase 2 Trial. PubMed. January 13, 2022. Accessed March 7, 2022. 

https://pubmed.ncbi.nlm.nih.gov/35025062/

Deucravacitinib is a possible solution for patients with psoriasis who wish to have the convenience of an oral medication.