The neuron with cell body, long axon, and dendrite with synaptic space (bright area)Most of the dementia drugs presently prescribed are cholinesterase inhibitors. To understand how this works in the brain, we have to learn how the neurons function. We have over 100 billion neurons in our brain. Neurons are the message relaying cells. They consist of a cell body that houses the nucleus , mitochondria, and other important systems that keep the neuron alive. Each neuron also has an axon, which is a long “conducting” tube that extends from the cell body. At the end of the axon are the dendrites or “small branches” that extend into the space between the dendrites of the next neuron. The neurons don’t physically touch each other, so how does the electronic message get from one neuron to the other?
In order for a signal to travel from one neuron to another, the dendritic ends of one neuron release sacs of chemicals that then flow and bind to the next neuron’s dendrites, thus relaying the message (bright area in the accompanying photo). These sacs of chemicals are called neurotransmitters. Some neurotransmitters excite the next dendrites and some may inhibit them – it’s like a key that opens a lock….or not. After the neurotransmitter is released and serves it’s function, it can be degraded by an enzyme, drift away, or may be reabsorbed by the releasing axon.
There are more than 100 chemicals that have been identified that play the role of neurotransmitter. They can be either excitory or inhibitory depending on their function and where they are located. [Excitory: glutamate, epinephrine, and norepinephrine Inhibitory: seratonin and gamma aminobutyric acid (GABA)]. Some chemicals can act as either excitory or inhibitory depending on the site: acetylcholine, and dopamine.
What is a cholinesterase inhibitor? When you see the suffix “ase” it means that it is an enzyme, it’s function is to break things apart. In other words a cholinesterase protein is an enzyme that cleaves the acetylcholine molecule such that it no longer can perform it’s function.
Subjects who have Alzheimer’s Disease have a lower concentration of acetylcholine in the synaptic spaces, therefore by preventing the naturally occuring enzyme from destroying the acetylcholine, it increases the presence and duration of the acetylcholine in the spaces. This allows better message transmission.
Drugs Prescribed For Dementia:
1) Cognex (tacrine Hcl) – This was the first drug tried for dementia patients but has been discontinued in the US due to liver toxicity side effects. Other adverse symptoms were nausea, vomiting, dyspepsia, diarrhea, & weight loss.
2) Aricept (donepezil) – Aricept was approved in 1996 by the FDA. It is a central acetylcholinesterase inhibitor. Some people experience diarrhea, stomach upset/pain, ulcers (GI bleed). Because of the GI symptoms some patients cannot take the drug.
3) Exelon (rivastigmine) – Rivastigmine is in the same family of drugs as Aricept, an acetylcholinesterase/butyrcholinesterase inhibitor. It was approved in 1997 in pill form and as a trans-dermal patch in 2007. The patch is especially useful for those patients who have stomach upset/pain issues on the pill form because it is absorbed through the skin rather than the stomach…therefore, less GI side effects.
4) Reminyl (galantamine) – Galantamine was approved by the FDA in 2001. It blocks the acetylcholinesterase enzyme from working. Reminyl was renamed Razadyne in 2005 because it and a diabetes medication had similar sounding names and prescription errors had occurred.
5) Namenda (memantine) – Memantine blocks glutamate. In Alzheimer’s Disease there is a hyperactivity of glutamate receptors, thus a blocker of glutamate holds promise. . It was approved in 2000 and made by Forest Labs. It was prescribed initially for later stage dementia.
6) Namzaric (donepezil + memantine in one) – Because most patients with dementia are prescribed both donepezil and memantine, they combined them into one tablet. It was also a way when memantine was going off patent to create another drug that can be under patent and thus be higher priced.
Side Effects of the Cholinesterase Inhibitors:
Nausea, diarrhea, vomiting, muscle cramps, light headedness, fainting (slow heart rate), headache, insomnia, skin irritation, and frequent urination may be present.
The above drugs may help to improve memory, and daily functioning in some people affected with dementia, but they are definitely not a cure. The drugs may help the person perform a little bit better a little longer, but in the end the decline is usually fairly rapid. They do not usually extend life. The cholinesterase inhibitors do not have much value in end stage dementia. Once the person reaches the end stages of the disease, most physicians will discontinue these medicines.