Prascend® (Pergolide) for Horses with PPID: Mechanism, Dosage & Side Effects

Pergolide mesylate (Prascend®) is a medication used to treat horses with pituitary pars intermedia dysfunction (PPID), previously referred to as Equine Cushing’s disease.

This common endocrine disorder, typically observed in older horses, can cause tendon and ligament breakdown, abdominal wall weakness, tooth loosening, depressed immune function, altered temperature regulation, increased coat length, poor shedding, and insulin resistance with laminitis.

It is estimated that between 20 and 30% of horses and ponies develop PPID by the time they are 20 years old. PPID is progressive and neurodegenerative, resulting in serious complications without proper management. ^[1]

While there is no known cure for PPID, its symptoms can be managed with medication and proper care. According to research, 75 – 100% of horses with PPID that are treated with pergolide experience an improvement in symptoms. ^[2][3]

Prascend® is the only FDA-approved treatment for horses with PPID. ^[1][4] If your horse has been diagnosed PPID, consult with your veterinarian to determine if Prascend® is appropriate treatment.

Pergolide Mesylate (Prascend®) for Horses

Prascend® is a brand name for the medication pergolide mesylate, manufactured by Boehringer Ingelheim Vetmedica. It is available in tablet form and is administered orally to horses with Pituitary Pars Intermedia Dysfunction (PPID) .

Pergolide mesylate is derived from ergotamine, a natural compound present in the ergot fungus (Claviceps purpurea). This drug acts as a dopamine agonist, binding to receptors on neurons and increasing dopaminergic activity in the brain. ^[5]

By mimicking the effects of dopamine, pergolide counteracts some of the effects of PPID and inhibits the excessive release of adrenocorticotropic hormone (ACTH), beta-endorphin and melanocyte stimulating hormone as well as their intermediates. This can minimize symptoms and slow disease progression. ^[1]

Clinical trials show that pergolide promotes normal hair growth and alleviates muscle wasting in affected horses. This drug also helps to increase energy levels and improves body condition in horses with PPID. ^[6]

Pergolide for Horses with PPID

Pergolide offers significant benefits in managing horses with PPID and improving their well-being.

PPID occurs due to the gradual loss of dopaminergic neurons in the hypothalamus of the brain, leading to a decline in dopamine production. The precise cause of the oxidative stress behind this degeneration is unknown.

PPID Pathophysiology

Dopamine plays important roles in the central nervous system and is involved in regulating hormone levels. ^[7] Specifically, dopamine regulates the release of ACTH and other hormones from the intermediate lobe of the pituitary. ^[4] ACTH is normally produced in the anterior pituitary where it’s release is inhibited by high levels of cortisol in the blood.

In horses with PPID, a lack of dopamine disrupts regulation of ACTH. As a result, the pituitary gland overproduces ACTH, which then stimulates the adrenal glands to produce excessive amounts of cortisol. ^[4]

Cortisol is a stress hormone that affects various body systems and contributes to the characteristic clinical signs observed in horses with PPID.

PPID Symptoms

Understanding the signs and symptoms of PPID is crucial for timely detection and effective management.

This complex hormonal disorder can manifest in various ways, with common symptoms including: ^[3][4]

• Hirsutism – excessive & abnormal hair growth, typically presenting as a long, curly coat
• Delayed shedding
• Pot belly
• Weight loss
• Muscle wasting & loss of topline
• Excessive thirst and urination
• Compromised immune function leading to frequent infections
• Excessive sweating
• Sinusitis
• Tooth loosening
• Frequent infections (often oral, pulmonary or dermal)
• Tendon and ligament weakening

Laminitis, also known as founder, is a condition that can develop secondary to PPID. This painful inflammatory condition is characterized by damage to the laminae of the hoof.

Repeated laminitis episodes can lead to severe lameness over time.

Diagnosis

PPID is typically diagnosed by physical examination and specific diagnostic tests. Early signs may be a first-in-lifetime laminitis in the fall or unexplained tendon and ligament problems.

The classical clinical signs of excessive, curly hair growth and delayed shedding, can indicate PPID but these are seen in advanced disease.

Although there is no single test that can offer a definitive diagnosis for PPID, common diagnostic procedures include a thyrotropin-releasing hormone (TRH) response test and measurements of basal plasma ACTH concentration. These tests help evaluate hormone levels and provide valuable insights into the presence of PPID. ^[4][14]

Despite increased cortisol production, plasma cortisol levels may or may not be elevated in horses with PPID. Removal of cortisol from the blood may also be affected. Therefore, plasma cortisol levels are not typically used for diagnosis of PPID. ^[8]

Pergolide Benefits

Pergolide acts as a dopamine D2 receptor agonist, compensating for the impaired dopamine signaling seen in horses with PPID. ^[5]

This activation of dopamine receptors inhibits the excessive release of ACTH from the pituitary gland. Through the suppression of ACTH release, pergolide improves regulation of cortisol production and better overall hormonal balance. ^[3]

Treatment with pergolide shows significant clinical benefits in horses with PPID, with one study reporting a 76.1% success rate in PPID horses. ^[9] Pergolide has also been found to return ACTH concentrations to normal levels in 28 – 74% of cases. ^[2]

Based on unpublished data by the ECIR group, administration at doses considerably above the recommended level is often needed to control the disease.

Researchers also report improvements in the following clinical signs within 3 – 6 months of beginning treatment: ^[9]

• Hirsutism (excessive hair growth)
• Polyuria (frequent urination)
• Polydipsia (excessive thirst)
• Delayed shedding
• Abnormal fat distribution
• Muscle wasting

Dosage & Administration

Seek guidance from a veterinarian before administering any medications, including pergolide, to your horse. Your veterinarian will be able to determine the appropriate dosage and provide specific instructions based on your horse’s condition and body weight.

Before starting pergolide treatment, your veterinarian will assess your horse’s baseline endocrine values, including basal ACTH levels. This establishes a starting point for treatment and allows veterinarians and horse owners to monitor the horse’s progress throughout the treatment period.

Pergolide is administered orally either by placing the tablet directly into the horse’s mouth or mixing it with their feed.

How Much Pergolide to Give to Horses

Pergolide is typically administered to horses at a dosage of 2 micrograms (ug) per kilogram of body weight. The recommended dose is determined by PPID progression and clinical signs. ^[5][10]

Here are the common pergolide dosages for horses of different body weights:

 
If the horse’s symptoms do not improve within 4-8 weeks, your veterinarian may recommend increasing the dose by 1 or 2 µg/kg monthly, up to a maximum of 10 µg/kg per day, until symptoms are effectively managed. ^[5][11] Advanced cases may require even higher doses.

Owners should closely monitor their horse’s behaviors, symptoms, and body condition during pergolide treatment. Regular endocrine testing may be recommended to assess effectiveness and to make any necessary adjustments.

How to Administer Pergolide

Due to their small size, Prascend® tablets can easily be lost within your horse’s feed and bedding. This can make it challenging to determine whether your horse has taken their medication.

Instead of adding Prascend® to your horse’s concentrates or supplements, try hiding medication in low-sugar treats, pill capsules or a handful of palatable low-sugar feed.

Some horse owners dissolve pergolide tablets into water and add it into soaked feed, or syringe the solution directly into the horse’s mouth. This helps ensure that all of the medication is consumed.

If you happen to miss a dose, administer it as soon as you remember, so long as it is not too close to your horse’s next scheduled dose. It’s important not to double-dose pergolide if you forget to give a dose.

Consult with your veterinarian if you have questions or concerns about administering pergolide to your horse.

Precautions

Prascend® should not be used to treat horses with a sensitivity to pergolide mesylate or other ergot substances. ^[5]

There is a lack of research on the effects of pergolide on mares in foal. This drug should only be used in pregnant or lactating mares if the benefits outweigh any potential risks, under the recommendation of a veterinarian.

To minimize potential side effects, administer pergolide to horses at the lowest effective dose possible.

Horses younger than 2 years old should not be given pergolide unless specifically instructed to do so by a veterinarian.

Interactions and Contraindications

Pergolide should not be give to horses on dopamine antagonist medications, such as acepromazine, sulpiride, domperidone or perphenazine, because these drugs have opposing effects on dopamine receptors. ^[5][12]

It is typically recommended to avoid using pergolide in conjunction with other drugs that affect protein binding. ^[5] However, in reality, the dosages used as so small there is unlikely to be any effect.

Side Effects

Prascend® is generally well tolerated by horses when administered at the appropriate dosage. However, horses may experience some potential side effects, which can include changes in behavior or decreased appetite.

Some horses experience a complete loss of appetite (anorexia) when starting treatment with pergolide mesylate. In these cases, it is recommended to temporarily discontinue treatment for a period of 2-3 days, after which pergolide can be reintroduced at a lower dose. ^[6]

If your horse is experiencing this side effect, consult with your veterinarian regarding feeding an adaptogen such as Jiaogulan. Starting this a few days prior to beginning the drug may help reduce this side effect.

Horses may appear dull, depressed or lethargic after starting pergolide treatment. This impact on mood may be explained by changes in dopamine signaling in the brain. Side effects typically disappear within 1 to 4 weeks.

Other rare reported side effects include: ^[5]

• Ataxia (loss of coordination)
• Colic
• Diarrhea
• Sweating

If you notice any concerning behavioral changes in your horse after starting pergolide, consult with your veterinarian. Dosing adjustments or additional supportive measures may be recommended to address any concerns.

Other Treatments for PPID

Prascend® is the only approved treatment for the management of PPID in horses. However, other medications may be recommended by your veterinarian depending on the individual needs of your horse.

• Cyproheptadine hydrochloride: This serotonin agonist is considered less effective than pergolide for treating PPID. ^[3][6]
• Trilostane: This synthetic steroid inhibits an enzyme (3-beta hydroxysteroid dehydrogenase) that plays an important role in cortisol production. It shows promise as a treatment for the insulin resistance in PPID and may help minimize clinical signs, especially laminitis. However, other hormones increased in PPID can also influence insulin resistance and may not be affected by trilostane. ^[3]
• Bromocriptine: This dopamine receptor agonist has a similar mechanism of action to pergolide, but is difficult to obtain and less convenient. Due to its low oral bioavailability, it is often administered multiple times a day via subcutaneous injection. In the EU, it is given orally twice a day.
• Combination Therapy: Some horses with PPID that do not respond well to recommended doses of pergolide are suggested to try multimodal therapy, involving a combination of treatments. Pergolide and cyproheptadine are often administered together to treat advanced cases of PPID. ^[6] However, there is no evidence this combination is more effective.

Nutritional Support for PPID Horses

While diet alone cannot treat PPID, a forage-based diet that provides sufficient vitamins and minerals can help support the overall health of horses with this condition.

These horses benefit from a diet that is low in sugars and starches, also known as hydrolyzable carbohydrates (HC). Avoid feeding energy-dense grains to reduce the risk of metabolic dysfunction and laminitis.

For more nutrition considerations, read our guide to Feeding a Horse with PPID.

Chasteberry

Chasteberry (Vitex agnus-castus) is a herbal supplement that is used to support hormone balance in horses with early PPID. Chasteberry is thought to influence dopamine activity in the brain. ^[13]

Studies suggest that chasteberry may help with symptoms commonly observed in horses with PPID, such as excessive hair growth and abnormal shedding. ^[13]

While chasteberry may have some positive effects on horses with PPID, it does not have the same ability as pergolide to lower ACTH levels. For this reason, pergolide is more effective in managing advanced cases of PPID. Chasteberry and pergolide should not be given together because of the potential for interference with pergolide function.

Summary

• Pergolide mesylate (Prascend®) is a dopamine agonist medication used to treat Pituitary Pars Intermedia Dysfunction in horses.
• Daily administration of pergolide can help manage symptoms associated with PPID, including abnormal hair coat, increased thirst and urination, weight loss, and muscle wasting.
• Consult with your veterinarian to determine the appropriate pergolide dosage for your horse.
• Pergolide is generally well tolerated but may cause side effects such as reduced appetite. Adverse reactions can usually be managed by adjusting the dosage, starting with a lower dose and gradually increasing, and with time.
• Horses with PPID benefit from a holistic approach to treatment, including dietary modifications to support overall health.