(for veterinary information only)
L-DEPRENYL HYDROCHLORIDE SELEGILINE HYDROCHLORIDE
BRAND NAME: ANIPRYL, ELDEPRYL, CARBEX
Monoamine oxidases are enzymes we have in two areas: the brain (monoamine oxidase inhibitor -B) and in the liver/GI tract (monoamine oxidase inhibitor -A). In the brain, these enzymes break down used neurotransmitters (chemicals that enable nerves to communicate). One of these neurotransmitters is called dopamine. Type B monoamine oxidases are responsible for getting rid of dopamine when it is no longer needed. Sometimes, however, it is beneficial to have dopamine stick around a bit. L-Deprenyl is a type B monoamine oxidase inhibitor (or MAO-B inhibitor) which is how it exerts its therapeutic effects.
There are two approved indications for L-Deprenyl in dogs: the treatment of Cushing’s disease, an excess in corticosteroid hormone production, and the treatment of senile mental deterioration (canine cognitive dysfunction). The use of L-Deprenyl in dogs with Cushing's disease has met with limited success despite its FDA approval for this use. Since trilostane and lysodren are virtually the only medications used for Cushing's disease, we will confine our discussion to the behavioral uses of L-Deprenyl. L-Deprenyl is not approved for use in cats but studies have shown it to be helpful in feline cognitive dysfunction as well.
Cushing’s disease is the insidious debilitating hormone imbalance that results when the adrenal glands overproduce cortisone. Most cases (85%) occur as the result of a tumor in the pituitary gland that produces a stimulatory hormone called ACTH. This hormone leads both adrenal glands to enlarge and overproduce cortisone, which in turn leads to symptoms associated with Cushing’s disease.
Treatment has traditionally centered on suppressing adrenal gland production and release of cortisone but this approach has been fraught with potential for side effects. L-Deprenyl has allowed for a new approach by suppressing the pituitary gland directly.
Monoamine oxidases are enzymes we have in two areas: the brain (monoamine oxidase inhibitor -B) and in the liver/GI tract (monoamine oxidase inhibitor-A). In the brain, these enzymes break down used neurotransmitters (chemicals that enable nerves to communicate). One of these neurotransmitters is called dopamine and one of its functions is the regulation, specifically the inhibition, of ACTH.
By using a monoamine oxidase-B inhibitor, dopamine is not broken down; instead, it persists and provides extra inhibition of ACTH. L-Deprenyl further acts on the enzymes that produce dopamine so that more dopamine is produced.
L-Deprenyl is a monoamine oxidase inhibitor specific to the brain’s monoamine oxidases; those of the liver/GI tract are not affected. This effect on ACTH inhibition allows for the treatment of pituitary dependent Cushing’s disease in dogs as well as the treatment of Parkinson’s syndrome in humans.
Because of the unique way that L-Deprenyl works as treatment for Cushing’s disease, the usual tests needed/used to monitor response to therapy will not be relevant. Assessment of effect is solely by the owner’s perception of improvement in symptoms. There is presently no way to determine prior to treatment if a dog has a pars intermedia tumor which is likely to respond to L-Deprenyl but it is generally clear if a dog is responding or not within 3 months of therapy (see below).
An additional effect of L-Deprenyl stems from an interaction with brain enzymes that destroy free radicals. By helping to rid the brain of destructive free radicals, L-Deprenyl has proven useful in treating Parkinson’s disease in humans as well as canine cognitive dysfunction (senility) in dogs. L-Deprenyl was approved in the dog first for the treatment of Cushing’s disease but has since been approved for the treatment of canine cognitive dysfunction.
CANINE COGNITIVE DYSFUNCTION
Pet owners have long been frustrated by age-related behavior problems involving loss of house-training, apparent memory loss or disorientation, sleep disturbances (either waking at the wrong time or sleeping unusually deeply) and loss of interest in social activities with the family. Such behavior changes are often written off as being normal aging. One study at the University of California Davis School of Veterinary Medicine demonstrates how common these observations are: out of 69 dogs participating, 32% of 11 year old dogs were affected by this syndrome and that 100% of dogs 16 years of age older were affected.
Still, the high frequency with which the syndrome is seen in older dogs does not make it normal. Other studies have shown that dogs affected by this syndrome show deposition of a protein called amyloid in their brains in patterns similar to the amyloid plaques found in the brains of humans with Alzheimer’s disease.
Cognitive dysfunction is associated with depletion of dopamine, the neurotransmitter mentioned above. As described above, L-Deprenyl also helps prolong dopamine activity, which may account for part of its efficacy in treating cognitive dysfunction. Further, dopamine breakdown results in harmful biochemicals known as free radicals. The use of L-Deprenyl also helps reduce amounts of free radicals in the brain.
HOW THIS MEDICATION IS USED
L-Deprenyl is given once a day for two months. If no response is seen in this time, the dose is doubled for an additional month. If still no response is seen, another form of treatment should be pursued. Of the 69 dogs with cognitive dysfunction mentioned above, approximately 76% showed improvement on L-deprenyl after one month of therapy. Some dogs improve in the first few days or weeks, some dogs do not show improvement until the second month. Often dogs would continue to improve during the first three months.
here is a 5% incidence of unacceptable side effects with L-Deprenyl treatment. These side effects include: vomiting, diarrhea, appetite loss, itchy skin, tremors, drooling, listlessness, disorientation, diminished hearing, or restlessness.
When three times the recommended dose was used in dogs, salivation, weight loss, panting, dehydration, pacing, and poor pupil response to light were observed. Obviously these signs should not be observed with normal use of the medication.
It should be noted that after oral administration, L-Deprenyl is processed by the liver to produce amphetamine and methamphetamine, both of which are stimulants.
INTERACTIONS WITH OTHER DRUG
L-Deprenyl has been used in conjunction with alprazolam and propranolol for phobias.
Serotonin syndrome is a potential side effect that can occur if brain levels of serotonin get too high. Elevated heart rate, tremors/shivering, dilated pupils, difficulty breathing, elevated body temperature, or high blood pressure can all be signs of serotonin syndrome. Animals with serotonin syndrome sometimes demonstrate general hyperactivity as a sign that something is wrong. Death can result if blood pressure rises too high. Because of this syndrome, medications that elevate serotonin levels should not be combined. The following interactions are avoided to prevent the possibility of serotonin syndrome.
For More Information on Canine Cognitive Dysfunction, visit: www.veterinarypartner.com/Content.plx?P=A&S=0&C=0&A=2549
Page last updated: 11/26/2017