From the Guidelines
Neurotonic or neuroprotective drugs have shown limited effectiveness in clinical trials for the treatment of stroke, with most studies producing disappointing results and some treatments even resulting in poorer outcomes or unacceptable rates of adverse experiences 1.
Definition and Mechanism
Neurotonic or neuroprotective drugs are medications designed to protect neurons from damage, degeneration, or death caused by various neurological conditions. These drugs work by preventing or slowing the progression of neuronal damage through multiple mechanisms, including regulating glutamate activity, increasing acetylcholine levels, reducing oxidative stress, and minimizing inflammation.
Examples of Neuroprotective Drugs
Some examples of neuroprotective medications include:
- Memantine and cholinesterase inhibitors (donepezil, rivastigmine, galantamine) for Alzheimer's disease
- Antioxidants like vitamin E and coenzyme Q10 to reduce oxidative stress
- Anti-inflammatory agents such as minocycline to reduce neuroinflammation
- Tissue plasminogen activator (tPA) for stroke patients to restore blood flow when administered within 4.5 hours of symptom onset
- Riluzole for ALS, which blocks glutamate release
- Certain anticonvulsants that stabilize neuronal membranes
Clinical Trial Results
Despite the potential benefits of neuroprotective drugs, clinical trials have yielded largely negative results. A 2013 guideline from the American Heart Association/American Stroke Association found that most clinical trials testing neuroprotective therapies have produced disappointing results, with some treatments resulting in worse outcomes or unacceptable rates of adverse events 1. Similarly, a 2007 guideline from the American Heart Association/American Stroke Association reported that numerous interventions have shown promise in experimental studies, but most clinical trials have produced negative results 1.
Recommendation
Based on the most recent and highest quality evidence, the use of neurotonic or neuroprotective drugs for the treatment of stroke is not recommended, except for tissue plasminogen activator (tPA) which should be administered within 4.5 hours of symptom onset 1.
From the Research
Definition of Neurotonic Drugs
Neurotonic drugs, also known as neuroprotective drugs, are medications that aim to protect the brain and nervous system from damage or degeneration.
Examples of Neurotonic Drugs
- Vinpocetine, an anti-epileptic drug, has been shown to effectively inhibit the rise in Ca(2+) induced by 4-AP in hippocampal isolated nerve endings 2.
- Sertraline, an anti-depressant, has also been found to inhibit the rise in Ca(2+) induced by 4-AP, suggesting its potential as a neurotonic drug 2.
- Other anti-epileptic drugs such as carbamazepine, phenytoin, lamotrigine, and oxcarbazepine have also been found to inhibit the rise in Ca(2+) induced by 4-AP, although at higher concentrations than sertraline and vinpocetine 2.
Mechanism of Action
The mechanism of action of neurotonic drugs can vary, but some may work by targeting presynaptic Na(+) and/or Ca(2+) channels in the brain, such as vinpocetine and sertraline 2. Others may have different mechanisms of action, such as selective serotonin reuptake inhibitors (SSRIs) which have become the most often prescribed antidepressants 3.
Potential Applications
Neurotonic drugs may have potential applications in the treatment of various neurological diseases and disorders, such as:
- Depersonalization disorder, where opioid receptor antagonists such as naltrexone and naloxone have been found to be useful in at least a subgroup of patients 4.
- Bipolar disorder, where patients are frequently treated with polypharmacy, and understanding pharmacokinetic and pharmacodynamic drug-drug interactions is crucial to avoiding adverse drug reactions 5.
- Neurological diseases and disorders, such as Alzheimer's disease and depression, where adult neurogenesis and neural stem cell research may lead to the discovery and development of novel neurogenic drugs 6.