Small Animal/Exotics
PHARM PROFILE
SELEGILINE
Sandy Calves, RPh, PharmD Candidate
Oregon State University/Oregon Health
Sciences University
S
elegiline is a monoamine oxi-
dase (MAO) inhibitor labeled
for the management of Parkin-
son’s disease in humans. In addition,
small studies investigating the use of
selegiline in Alzheimer patients have
shown that it has beneficial effects
on cognitive function and behavioral
performance.1,2
PHARMACOLOGY
Monoamine oxidase, an enzyme
found in the brain, liver, and kidney,
normally metabolizes catecholamines
(norepinephrine, epinephrine, dopa-
mine, and serotonin) for excretion in
urine. MAO has two subtypes: A and
B.3 Selegiline irreversibly binds to the
active site of MAO-B; consequently,
natural substrates (i.e., the catechol-
amines) cannot bind and thus the
amount of central and circulating cat-
echolamines increases. Because sele-
giline prevents the breakdown and
excretion of catecholamines, dopa-
minergic activity increases.4
Two mechanisms of action have
been proposed for selegiline: (1) pres-
ervation of neuronal dopamine via
selective inhibition of MAO-B, and
(2) inhibition of dopamine reuptake
and increased dopamine synthesis via
Pharm Profile introduces drugs that are new to the veterinary market as well as new indications for existing drugs. If you would like
Pharm Profile to cover a particular agent, please contact column editor Gigi Davidson, BS, RPh, North Carolina State University,
4700 Hillsborough Street, Raleigh, NC 27606; phone 919-821-9500 • fax 919-829-4225 • email gigi_davidson@ncsu.edu.
blockade of the presynaptic dopa-
mine receptors responsible for regu-
lating dopamine synthesis.3
Selegiline demonstrates a dose-de-
pendent effect. As the dose increases,
MAO-B activity decreases and the
amount of dopamine in the system
increases.5
Evidence suggests that dopamine
deficiency plays a role in the patho-
physiology of pituitary-dependent hy-
peradrenocorticism (PDH).6 Because
selegiline blocks dopamine break-
down, dopamine release in the brain
is enhanced and clinical signs of
PDH are improved. Selegiline treat-
ment has been shown to resolve many
of the behavioral abnormalities asso-
ciated with PDH.6
Researchers have also investigated
the effects of selegiline on life pro-
longation. One study7 showed that
healthy, 10- to 15-year-old dogs re-
ceiving 1 mg/kg selegiline for at least
6 months had higher survival rates com-
pared with dogs receiving a placebo.
Although large-scale clinical trials
need to be performed to further in-
vestigate these findings, these data
along with those from studies con-
ducted in rodents8 suggest that se-
legiline may enhance longevity.7
Compendium March 2000
INDICATIONS
Selegiline is indicated for use in
dogs to control signs associated with
canine cognitive dysfunction syndrome
and uncomplicated PDH.8
CAUTIONS
Selegiline is contraindicated in pa-
tients with known hypersensitivity to
MAO inhibitors.6,8,9
Adverse Reactions
Overall, selegiline is well tolerated.
Dogs have rarely been withdrawn from
trials because of adverse effects associat-
ed with the drug. Gastrointestinal dis-
turbances, particularly vomiting and
diarrhea, are the most common side ef-
fects reported.2,6,8 Diarrhea may resolve
when the drug is discontinued or the
dose decreased.6 Other adverse effects
include hyperactivity, agitation, rest-
lessness, and insomnia. A dose reduc-
tion or discontinuation of therapy also
resolves these problems.2,8
Use in Pregnancy
Selegiline is labeled as pregnancy
category C in humans.1 No reported
studies have evaluated the safety of
selegiline in pregnant and lactating
humans or bitches.6,8
Compendium March 2000
ACUTE TOXICITY
The maximum daily dose of se-
legiline in dogs is 2 mg/kg. Dogs
that received 3 or 6 mg/kg/day for 6
months experienced hypersalivation,
decreased pupillary response, and
weight loss despite a normal ap-
petite. Dogs receiving 3 mg/kg/day
exhibited repetitive movement be-
haviors (i.e., repeatedly moving left
to right in the cage). There are no re-
ports of blood pressure, heart rate, or
ophthalmic changes in dogs receiv-
ing selegiline.8 Orthostatic hypoten-
sion, resolvable with a decrease in
dose or discontinuation of therapy,
has rarely been reported in humans
treated with selegiline.2
DRUG INTERACTIONS
Concurrent use with meperidine is
contraindicated because increased
toxicity—manifested as agitation,
delirium, cardiovascular instability,
hyperpyrexia, and death—has oc-
curred in humans who received this
drug combination.9 Central nervous
system toxicity and serotonin syn-
drome may occur when selegiline is
used in conjunction with selective
serotonin reuptake inhibitors (e.g.,
fluoxetine), nonspecific MAO in-
hibitors, or tricyclic antidepres-
sants.8,9 Serotonin syndrome is a po-
tentially fatal condition characterized
by increased blood pressure, tremor,
altered mental status, hyperreflexia,
hyperthermia, and restlessness. 9
These interactions have not been
documented in dogs, but avoidance of
such combinations is recommended.6,8
DOSAGE AND ADMINISTRATION
The recommended dose for dogs
with canine cognitive dysfunction syn-
drome is 0.5 to 1 mg/kg orally, ad-
ministered each morning.8 Drug ther-
apy in dogs diagnosed with PDH
should begin at 1 mg/kg orally once
daily6,8 and continue for 2 months.
Patients should be monitored for clin-
ical efficacy periodically during this
initial period; response to treatment
Small Animal/Exotics
Client Counseling Information
■ Selegiline may be given with or without food.
■ Store selegiline at room temperature but not in the kitchen or bathroom
(extreme temperatures or humidity may deactivate the drug).
■ Follow your veterinarian’s recommendations concerning doses and
administration.
■ See your veterinarian regularly so that your pet’s response to treatment
can be monitored.
■ Because selegiline may cause behavior alterations that might not be
observed during an office visit, watch your dog for any changes in mental
status, weight loss despite increased food consumption, repetitive behavior,
hypersalivation, altered sleep and activity levels, and excessive vomiting or
diarrhea. Report the occurrence of these signs to your veterinarian.
can be evaluated based on physical clinically.6 These results suggest that
examinations and owners’ reports of low-dose dexamethasone testing may
patient behavior. If no improvement not accurately reflect the overall effi-
is seen after 2 months of therapy, the cacy of selegiline.
dose can be increased to 2 mg/kg/
day. If clinical signs still have not im- PREPARATIONS
proved after a patient has received 2 Anipryl® (Pfizer Animal Health, Ex-
mg/kg/day for 1 month, alternative ton, PA) is available in 2-, 5-, 10-, 15-,
therapy or further evaluation for the and 30-mg tablets.8
presence of other disease should be
considered.6 Studies have shown that STORAGE AND HANDLING
most patients continue to show signs Selegiline should be stored at room
of improvement after 6 months of temperature (68°F to 77°F [20°C to
selegiline therapy.6 There are no data 25°C]) and protected from freezing
to suggest an optimal length of ther- temperatures, extreme heat, and mois-
apy beyond 6 months. ture.8 Extreme temperatures or hu-
midity may deactivate the drug. No
MONITORING special precautions are needed when
Dogs being treated with selegiline handling selegiline.9
should be monitored for improve-
ment in clinical signs (e.g., polyuria/
polydipsia, increased appetite and REFERENCES
1. Lacy C, Armstrong LL, Goldman MP:
weight gain, decreased activity, pant- Selegiline, in Drug Information Handbook,
ing, increased sleeping) and laborato- ed 7. Hudson, OH, Lexi-Comp, Inc. 1999,
ry abnormalities (e.g., increased se- pp 1110–1131.
rum alkaline phosphatase, increased 2. Tolbert SR, Fuller MA: Selegiline in treat-
leukocyte count, decreased urine spe- ment of behavioral and cognitive symp-
toms of Alzheimer disease. Ann Pharma-
cific gravity) associated with PDH.
cother 30:1122–1129, 1996.
No specific laboratory tests are re- 3. Mahmood I: Clinical pharmacokinetics
quired during treatment with selegi- and pharmacodynamics of selegiline: An
line.8 update. Clin Pharmacokinet 33(2):91–102,
Results of low-dose dexametha- 1997.
sone suppression testing were evalu- 4. Baldessarini RJ: Drugs and the treatment
of psychiatric disorders, in Hardman JH,
ated in a 6-month study investigating
Limbird LE, Molinoff PB, et al (eds):
the efficacy and toxicity of selegiline; Goodman and Gilman’s The Pharmaco-
although test results normalized in logical Basis of Therapeutics, ed 9. New
15% of dogs, 83% of dogs improved York, McGraw-Hill, 1996, pp 439–440.
Small Animal/Exotics
5. Milgram NW, Ivy MP, Murphy EH: Effects of chronic oral adminis-
tration of L -deprenyl in the dog. Pharm Biochem Behavior
51(2/3):421–428, 1995.
6. Bruyette DS, Ruehl WW, Entriken T: Management of canine pitu-
itary-dependent hyperadrenocorticism with L-deprenyl (Anipryl). Vet
Clin North Am Small Anim Pract 27(2):273–286, 1997.
Compendium March 2000
7. Product information: Anipryl®. Exton, PA, Pfizer Animal Health,
1998.
8. Ruehl WW, Entriken TL, Muggenburg BA: Treatment with L-de-
prenyl prolongs life in elderly dogs. Life Sci 61(11):103–144, 1997.
9. Selegiline: Drug evaluation monograph. Micromedex Health Care
Series, vol 97, exp 9/98, accessed 7/98.