L-Deprenyl

(for veterinary information only)

L-DEPRENYL HYDROCHLORIDE SELEGILINE HYDROCHLORIDE

BRAND NAME: ANIPRYL, ELDEPRYL, CARBEX

AVAILABLE IN            
2 mg, 5 mg, 10 mg, 15 mg, 30 mg
TABLETS                
sold in 30 tablet blister packs    

BACKGROUND

There are two uses for L-Deprenyl in dogs: the treatment of Cushing’s disease, an adrenal hormone imbalance, and the treatment of senile mental deterioration (canine cognitive dysfunction). We will discuss the applications in the treatment of Cushing’s disease first as this is what L-Deprenyl was first approved for in dogs.

CUSHING’S DISEASE

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.

Pituitary GlandThere is an important caveat in the use of L-Deprenyl for the treatment of Cushing’s disease. While 85% of dogs with Cushing’s disease have pituitary tumors, only about 20% of them have tumors in the pars intermedia of the pituitary gland which is where ACTH is dependent on dopamine. This means that if a dog with pituitary Cushing’s disease is not one of this 20% the only effect L-Deprenyl will have will be a general stimulatory effect from its metabolites (see below).

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

Dosing protocols are different depending on whether one is treating Cushing’s disease or Cognitive Dysfunction Syndrome. In treating Cushing’s disease, 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. Approximately 20% of dogs with Cushing’s disease will respond to L-Deprenyl.

A lower dose of L-Deprenyl is used in the treatment of canine cognitive dysfunction. Of the 69 dogs 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. If no improvement is seen after the first month, the dose is doubled for an additional one month before re-evaluating the patient for an underlying medical problem that could be causing the behavior problems.

SIDE EFFECTS

With previous treatments for Cushing’s syndrome, monitoring tests to avoid side effects were central to treatment. The beauty of treating Cushing’s syndrome with L-Deprenyl is that no monitoring tests are necessary. This is because adrenal function is not directly altered.

There 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 DRUGS

  • L-Deprenyl should not be used concurrently with amitraz (Mitaban dips, Preventic tick collars, or Promeris). Other forms of parasite control should be pursued as needed.
     
  • L-Deprenyl should not be used with fluoxetine. Because of fluoxetine’s ability to last a long time in the body, a 5-week period is recommended between the discontinuation of fluoxetine and the initiation of L-Deprenyl. Other psychoactive drugs not compatible with MAO-B inhibitors include mirtazapine, amitriptyline, and clomipramine.
     
  • L-Deprenyl should not be used in combination with phenylpropanolamine, a common medication used in the management of urinary incontinence in older dogs. If your dog is already on phenylpropanolamine and you wish to try L-Deprenyl, it is important to have discontinued phenylpropanolamine for at least 2 weeks before beginning L-Deprenyl. High blood pressure can result from the use of these two medications together.
     
  • In humans, dangerous drug interactions have occurred when L-Deprenyl has been combined with meperidine (Demerol®). It is unclear how dangerous other narcotic might be so it is recommended that no narcotic be combined with L-Deprenyl, especially not meperidine.

For More Information on Canine Cognitive Dysfunction, visit www.anipryl.com

For More Information on Cushing’s Disease, visit our Cushing’s Disease Center.

Page last updated: 9/9/10