Nicergoline/Hydergine Are Novel Drugs
Nicergoline and hydergine have novel mechanisms. Most dementia drugs are acetylcholinesterase inhibitors. They inhibit acetylcholinesterase which breaks down acetylcholine. The net effect is a boost in acetylcholine signaling. This strategy temporarily reduces the symptoms of dementia without changing the course of the disease.
The gold standard in Alzheimer’s research is a “disease-modifying treatment.”
In contrast to acetylcholinesterase inhibitors, the mechanism of action of nicergoline and hydergine are less cut-and-dry.
What’s known about hydergine is that it activates serotonin and dopamine receptors while blocking alpha-adrenergic signaling. Hydergine may also offset the increased MAO activity observed in aging.
Nicergoline is a selective and potent alpha-1A adrenergic receptor antagonist (with an IC50 of 0.2 nM). The primary mechanism of action of nicergoline is enhanced blood flow to the brain.
What are the key differences between nicergoline verses Hydergine? Here’s a quick-and-dirty comparison.
Nicergoline vs Hydergine Comparison Table
|Treats||Senile dementia, vascular disorders (e.g., Raynaud’s disease)||Dementia, stroke recovery|
|Legal status||Over-the-counter||Rx only|
|Half-life||13-20 h||3.5 h|
|Routes of administration||Oral, intramuscular, intravenous||Oral, parenteral|
|Metabolism||Liver (extensive first-pass metabolism)||_|
|Adverse effects||Nausea, hot flushes, mild gastric upset, hypotension and dizziness. High doses: bradycardia, increased appetite, agitation, and diarrhea.||Orthostatic hypotension, bradycardia, skin rash, flushing, blurred vision, nasal congestion, increased risk of fibrosis and ergotism.|
Dementia vs Alzheimer’s Disease
Dementia is the progressive decline in cognition. Alzheimer’s disease is one type of dementia; dementia is the broader category.
What are the signs of dementia? The following can be harbingers:
- cognitive, behavioral and psychological impairments
- increasing difficulty in performing regular activities in everyday life
Dementia can develop spontaneously or as a symptom of a neurological disease. The most common forms are Alzheimer’s disease (AD), which makes up 70% of cases, followed by vascular dementia, which makes up 10% of cases.
Nicergoline and to lesser extent hydergine are better choices for vascular dementia because they enhance blood flow.
The causes of dementia are not completely understood, but most cases involve the accumulation of a protein associated with nerve cell (neuron) loss. While there is no cure for dementia, many approaches have been developed to manage the symptoms.
Composition of Hydergine
One therapy, which holds a lot of promise, is ergoloid mesylates (trade name Hydergine). Ergoloid mesylates is actually not a pure substance; it’s a cocktail of three compounds:
- alpha- and beta-dihydroergocryptine
All of these are dihydrogenated ergot alkaloids derived from the fungus Ergot.
Hydergine has been used for all kinds of maladies for decades. But its primary use was for treatment of dementia symptoms related to the spontaneous decline in mental capacity.
The Food and Drug Administration (FDA) has approved the drug to be prescribed in 1mg doses taken three times a day. It can be administered in tablet form, in liquid form, or in liquid capsule form.
Hydergine Absorption and Metabolism
Approximately 25% of hydergine that is taken is absorbed into the bloodstream by the intestines. This low absorption rate may explain why the effects are not typically observed until 3-4 weeks later. The half-lives of the Hydergine and its metabolites are 4 and 13 hours, respectively. Peak concentrations, of Hydergine in the body, are achieved approximately 1.5-3 hours after ingestion.
Hydergine’s Mechanism of Action
The mechanism of how Hydergine improves cognition is still relatively unknown. It was previously thought that Hydergine increased blood flow to the brain. However, there is no conclusive evidence obtained to support this theory. More recent studies now suggest that Hydergine may function by modulating the release of chemical messengers in the brain called neurotransmitters.
Hydergine was once the leading drug in the treatment of dementia-related symptoms. However, due to varying patient responses in multiple clinical studies, it is no longer the go to treatment for symptoms of dementia. While patients with vascular dementia were more likely to experience benefits from the product, many non-vascular dementia patients reported no beneficial effects. Furthermore, patients that did see an improvement in their symptoms only responded to doses higher than the FDA recommended amount.
The Discovery of Nicergoline
Because of the inconsistent study results on the efficacy of ergoloid mesylates, researchers examined other ergot products to find more consistent and effective treatments of mental decline. This led to the discovery of nicergoline.
Nicergoline is an ergot derivative that became clinically available in the 1970s. Nicergoline was originally developed to treat cerebrovascular disorders; however, because it influences multiple mechanisms in the body, its use has been expanded to several other diseases and disorders. These include various forms of dementia, peripheral vascular disorders, balance disorders, and in rare cases Parkinson’s disease.
Nicergoline Has Greater Bioavailability Than Hydergine
In contrast to Hydergine, nicergoline is almost completely absorbed by the body. While it can take longer to reach maximal concentrations (3 hours) than Hydergine, nicergoline has a longer half-life, 15 hours. Another benefit to nicergoline is that it only needs to be taken twice a day.
Although not completely understood, the modes of action of nicergoline are more defined than those of Hydergine.
Nicergoline is involved in a number of processes that contribute to dementia symptom improvement. Nicergoline strongly interacts with a blood vessel constriction related protein called α1-adrenoceptors. Because nicergoline was originally designed to treat a vascular condition, it is not surprising that it blocks activation of the α1-adrenoceptor resulting in:
- dilation of blood vessels
- reduced blood flow resistance
- increased blood flow.
Nicergoline has also been shown to affect neurotransmitters in the brain.
Similar to hydergine, nicergoline modulates levels of catecholaminergic neurotransmitters by enhancing the removal of noradrenaline and dopamine.
The fight-or-flight response in the face of a threat or challenge also elicits dopamine and noradrenaline release.
Nicergoline also influences levels of another neurotransmitter, acetylcholine, in the hippocampus. This ia a region of the brain vital to learning and memory. As expected, treatment with nicergoline likely improves memory.
Nicergoline activates major signaling pathways. Moreover, it’s thought to influence neuronal activity and the synthesis of proteins that contribute to dementia related diseases.
It also stimulates release of nerve growth factor (NGF). NGF
- promotes nerve tissue growth
- protects neurons from degradation
- prevents the loss of cholinergic neurons
Lastly, nicergoline stimulates increased use of oxygen and glucose, a sugar that provides the body with energy, among the neuron cells.
Treatment with nicergoline has both short and long term effects. In the short term, nicergoline improves cognition and behavior in as little as two months. However, the longer treatments have a greater impact on dementia symptom reduction.
There are some drawbacks to nicergoline use. Patients who respond best to nicergoline tend to be younger with less severe symptoms than patients with low or no response.
Like hydergine, some studies found that patients with vascular dementia experienced more beneficial effects than patients with other types of dementia. However, other studies have not detected a difference in the effectiveness in patients with different forms of dementia.
Nicergoline vs Hydergine In Brief
In summary, as the elderly population grows, it is increasingly becoming important to find effective treatments for dementia.
While Hydergine benefits some patients with dementia, a more comprehensive treatment program is better.
With its multiple modes of attack, less cumbersome treatment schedule, and potential effectiveness in patients with different forms of dementia, nicergoline has provided a better alternative for treating symptoms of mental decline.