Permax (pergolide) / Eli Lilly - LARVOL DELTA

Effects of Dopamine Agonists on the Estradiol-Induced Prolactin Surge in Ovariectomized Female Wistar Han Rats. (PubMed, Toxicol Sci) - "We investigated the effects of 2 D2/D3 DAs, pergolide and rotigotine, on the estradiol (E2)-induced prolactin surge in ovariectomized (OVX) female Wistar Han rats...This study demonstrates the utility of the OVX rat model in evaluating the effects of DAs on the E2-induced prolactin surge. These results support the use of rotigotine, a DA with a long history of safe human use without significant endocrine-related adverse events, as a positive control at a dose level of 5.0 mg/kg/day for future nonclinical toxicity studies investigating the effects of novel DAs on reproductive hormones in rats."

Journal • Preclinical • CNS Disorders • Endocrine Cancer • Movement Disorders • Oncology • Parkinson's Disease • Restless Legs Syndrome • Sleep Disorder

Effect of pergolide treatment on insulin dysregulation in horses and ponies with pituitary pars intermedia dysfunction. (PubMed, Equine Vet J) - "Pergolide had no effect on tissue insulin sensitivity. However, the results suggest that postprandial hyperinsulinaemia may be limited by this dopamine receptor agonist in animals with PPID plus ID."

Journal

Pergolide mesylate administration does not decrease blood thyroid hormone concentrations and thyroid function in horses. (PubMed, Am J Vet Res) - "Protein-bound agents do not necessarily affect thyroid hormone concentrations. In horses with pituitary pars intermedia dysfunction, low thyroid hormone concentrations are likely due to the condition itself, not pergolide treatment."

Journal • Endocrine Disorders

Ergot alkaloid control in biotechnological processes and pharmaceuticals (a mini review). (PubMed, Front Toxicol) - "We reviewed analytical approaches for the determination of ergopeptines (including their dihydro- and bromine derivatives) and semisynthetic ergot-derived medicines such as cabergoline, necergoline and pergolide, including precursors for their synthesis. Both rapid methods and liquid chromatography remain in demand in routine practice, with rapid analysis evolving toward higher accuracy owing to improved analytical performance and new equipment. New composite electrochemical sensors (including disposable sensors) have demonstrated potential for real-time process control."

Journal • Review

Equine Pergolide Toxicity: A Case Series. (PubMed, Cureus) - "Veterinary medication ingestion presents a unique challenge to clinicians as the drug may have limited human toxicity data and/or recommended animal dosing may differ greatly from human dosing. Case reports of human toxicity may assist with anticipating the clinical course and guiding medical decision-making."

Journal • Cardiovascular • CNS Disorders • Cushing’s Disease • Endocrine Disorders • Heart Failure • Movement Disorders • Parkinson's Disease

In silico off-target profiling for enhanced drug safety assessment. (PubMed, Acta Pharm Sin B) - "Using the withdrawn drug Pergolide as an example, we elucidate the mechanisms underlying ADRs at the target level, contributing to the exploration of the potential clinical relevance of newly predicted off-target interactions. Overall, our work facilitates the early assessment of compound safety/toxicity based on off-target identification, deduces potential ADRs of drugs, and ultimately promotes the secure development of drugs."

Journal

Retrospective assessment of the use of extended-release cabergoline in the management of equine pituitary pars intermedia dysfunction. (PubMed, Front Vet Sci) - "Dopaminergic agonists are accepted as the most effective treatment for pituitary pars intermedia dysfunction. Clinical and endocrinological responses were consistent with results of previous reports of oral pergolide treatment. Weekly injection of ERC may be an effective alternative to pergolide; the 0.005 mg/kg dose appeared to be as effective, with less risk of inappetence, than the 0.01 mg/kg dose that has been reported previously."

Journal • Retrospective data

Metabolic and Endocrine Insights in Donkeys. (PubMed, Animals (Basel)) - "In donkeys with clinical signs of ID (obesity or recurrent laminitis) or PPID (hypertrichosis, regional adiposity, laminitis and weight loss), where these hormones are in the normal or non-diagnostic range (donkey-specific cut-off values and reference ranges need to be established), dynamic tests are recommended (oral sugar test or thyrotropin-releasing hormone, respectively). Equine treatment protocols apply to donkeys, although pharmacological studies for most drugs, except pergolide, are lacking."

Journal • Review • CNS Disorders • Dermatology • Endocrine Disorders • Genetic Disorders • Infectious Disease • Metabolic Disorders • Obesity

Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins. (PubMed, J Psychopharmacol) - "Concerningly, both LSD and psilocybin share structural similarities with medications which raise the risk of cardiac fibrosis and valvulopathy when taken regularly, including methysergide, pergolide, and fenfluramine. In this review, we evaluate the evidence that microdosing LSD, psilocybin, and other psychedelics for several months or more could raise the risk of cardiac fibrosis. We discuss the relationship between drug-induced cardiac fibrosis and the 5-HT2B receptor, and we make recommendations for evaluating the safety of microdosing psychedelics in future studies."

Journal • Review • Cardiovascular • Fibrosis • Immunology

Influence of feeding and other factors on adrenocorticotropin concentration and thyrotropin-releasing hormone stimulation test in horses and ponies. (PubMed, Equine Vet J) - "There was no evidence that feeding influences the b/pACTH. There was evidence that pergolide affects the bACTH but it had little effect on pACTH. Further investigation of the impact of month and coat colour on b/pACTH is warranted to better interpret the results."

Journal

BEVA primary care clinical guidelines: Diagnosis and management of equine pituitary pars intermedia dysfunction. (PubMed, Equine Vet J) - "These findings should be used to inform decision-making in equine primary care practice."

Clinical guideline • Journal • Review • Dermatology • Pain

Dopamine agonists versus levodopa monotherapy in early Parkinson's disease for the potential risks of motor complications: A network meta-analysis. (PubMed, Eur J Pharmacol) - "In the two non-ergot DAs, ropinirole is associated with a lower risk of dyskinesia while pramipexole is associated with lower risks of wearing-off and on-off fluctuations. Our research may facilitate head-to-head research, larger sample sizes, long following-up time RCTs to confirm the findings of this network meta-analysis."

Journal • Monotherapy • Retrospective data • CNS Disorders • Movement Disorders • Parkinson's Disease

Neuroprotective Effect of Celastrus Paniculatus Seed Extract on Epilepsy and Epilepsy-associated Cognitive Deficits. (PubMed, Basic Clin Neurosci) - "The present study evaluated the effect of Celastrus paniculatus seed extract on seizure severity and cognitive deficit following the pentylenetetrazole (PTZ)-induced chemical kindling model...After four weeks of induction, the following treatment, namely sodium valproic acid (SVA) 200 mg/kg, C. paniculatus 500 mgkg, pergolide 2 mg/kg, C. paniculatus (250 mgkg)+ Pergolide (1 mg/kg), and C. paniculatus (250 mgkg)+ SVA (100 mg/kg) were administered 30 minutes prior to PTZ (30 mg/kg) injection for a period of next 14 days...C. paniculatus alone and in combination with other agents may have the potential to treat epilepsy and associated cognitive deficits."

Journal • CNS Disorders • Cognitive Disorders • Epilepsy • CAT

Multimodal Imaging of Constrictive Pericarditis Induced by Long-term Pergolide Treatment for Parkinson's Disease. (PubMed, Intern Med) - "The treatment history of Parkinson's disease and pathological findings of the removed pericardium suggested that long-term pergolide was the cause of CP. Properly recognizing pergolide as the cause of CP and accurately diagnosing CP using multimodal imaging may contribute to the early detection and treatment of pergolide-induced CP."

Journal • Cardiovascular • CNS Disorders • Movement Disorders • Parkinson's Disease • Pulmonary Disease

Pharmacokinetic properties of pergolide mesylate following single and multiple-dose administration in donkeys (Equus asinus). (PubMed, Equine Vet J) - "Pergolide mesylate (dosed at 2 μg/kg bwt) is bioavailable in donkeys after intragastric and PO administration. Differences in pharmacokinetics were noted after multiple doses, likely related to different routes of administration and sublingual absorption of pergolide."

Journal • PK/PD data • Endocrine Disorders

Plasma Amino Acids in Horses Suffering from Pituitary Pars Intermedia Dysfunction. (PubMed, Animals (Basel)) - "Horses receiving pergolide with ACTH ≤ 30 pg/mL were allocated to the group PPIDrr (PPID, ACTH in reference range) and horses receiving pergolide with ACTH ≥ 100 pg/mL to the group PPIDarr (PPID, ACTH above reference range)...Arginine was significantly higher in PPIDrr than in PPID and nPPID, asparagine was significantly higher in PPID, PPIDrr, and PPIDarr than in nPPID, citrulline was significantly higher in PPIDrr than in nPPID and PPID, cysteine was significantly lower in PPIDrr than in PPID, nPPID, and PPIDarr, and glutamine was significantly higher in PPID and PPIDarr than in nPPID. Especially, asparagine, citrulline, and glutamine may be potential diagnostic markers and may offer interesting approaches for research regarding amino supplementation in PPID."

Journal • CNS Disorders • Endocrine Disorders • Movement Disorders • Parkinson's Disease

Effects of Anti-Parkinsonian Drugs on Verbal Fluency in Patients with Parkinson's Disease: A Network Meta-Analysis. (PubMed, Brain Sci) - "In terms of letter fluency, the ranking of the overall efficacy of included drug regimens was: levodopa, levodopa combined with pramipexole, rotigotine, cabergoline, pramipexole, pergolide, but no drug regimen presented a significant advantage over the others. Levodopa and rotigotine seem to be more appropriate choices for PD patients with verbal fluency impairment. Further study is needed to illustrate the efficacy of drugs on verbal fluency in PD patients."

Journal • Retrospective data • Review • CNS Disorders • Movement Disorders • Parkinson's Disease

Exploring the underlying mechanisms of drug-induced impulse control disorders: A pharmacovigilance-pharmacodynamic study. (PubMed, Psychiatry Clin Neurosci) - "Our results supported the role of D3-receptor agonism in inducing impulsivity in dopamine receptor agonists and identified a potential role of 5-HT1a receptor agonism in antipsychotics. Investigating these receptors may drive towards a better management of drug-induced impulsivity."

Adverse events • Journal • PK/PD data • Behavior Disorders • CNS Disorders

Targeting Immune Signaling in Genetic Models of Risk for Alcohol and Substance Abuse (ACNP 2022) - "Methods In separate studies, we examined (a) whether the HDID-1 and HDID-2 lines of mice would voluntarily consume the following drugs in a 4 day DID test: nicotine (30, 50, or 70ug/mL), midazolam (150ug/ml), methamphetamine (40ug/ml), and morphine (700ug/ml), (b) whether the HDID lines differed from their founder line, HS/NPT, in consumption levels of these drugs, and (c) whether compounds targeting immune signaling also reduce intake of nicotine or morphine in a 2 day DID (studies are underway to test additional drugs of abuse). (b) Terreic acid, pergolide, and apremilast significantly reduced nicotine (p’s<0.01) and morphine (p’s<0.01) intake in male and female HDID-1 and -2 mice. Conclusions Together, this work tells us that increasing anti-inflammatory signaling reduces excessive substance use in unique animal models that exhibit construct validity, face validity, and predictive validity for AUD and SUD."

Substance Abuse

Targeting Neuroimmune Signaling in Substance Use Disorders (ACNP 2022) - "Ozburn will present data showing that targeting immune signaling (via administration of terreic acid, pergolide, or apremilast) reduces excessive alcohol, nicotine, and morphine intake in genetic mouse models of risk for binge drinking. Dr. Mason presents data for the first clinical study of apremilast for the treatment of AUD."

Addiction (Opioid and Alcohol) • IL33 • IL6

Prospective Case Series of Clinical Signs and Adrenocorticotrophin (ACTH) Concentrations in Seven Horses Transitioning to Pituitary Pars Intermedia Dysfunction (PPID). (PubMed, Vet Sci) - "One horse was treated with pergolide which normalized basal ACTH concentrations...Horses transitioning to PPID can have subtle clinical signs and equivocal ACTH concentrations. However, TRH-stimulated ACTH concentrations can be markedly greater than DCOV, especially in late summer and early autumn (February and March) allowing for identification of subclinical and transitional cases."

Journal • Dermatology • POMC-null Obesity

Pituitary Pars Intermedia Dysfunction (PPID) in Horses. (PubMed, Vet Sci) - "Future research should be targeted at improving the accuracy of the diagnosis of PPID, as basal adrenocorticotropic hormone (ACTH) concentration can lack sensitivity and thyrotropin releasing hormone (TRH) used to assess ACTH response to TRH stimulation is not commercially available as a sterile registered product in many countries. The relationship between PPID and insulin dysregulation and its association with laminitis, as well as additional management practices and long-term responses to treatment with pergolide also require further investigation."

Journal • Review • Dermatology • POMC-null Obesity

Management of Pituitary Pars Intermedia Dysfunction in Practice: A Clinical Audit. (PubMed, Vet J) - "Only 77.7% (n=160/206) of pergolide-treated animals had documented PPID monitoring and of these, only 48.1% (n=77/160) had follow-up basal ACTH testing in the first 1-3 months following diagnosis. The findings confirm that management of PPID in veterinary practice fell below contemporaneous recommendations, especially for monitoring."

Journal • Dermatology • Endocrine Disorders

Adverse drug reactions to apomorphine: a worldwide pharmacovigilancedatabase analysis (MDS Congress 2022) - "Over the past 20 years, pharmacovigilance has played a major role in defining the safety profile of antiparkinsonian drugs under real-world conditions of use (e.g. sudden sleep attacks and levodopa, fulminant hepatitis and tolcapone, or valvular heart disease and pergolide)...Co-medications with other drugs (including levodopa, carbidopa, entacapone, trimethobenzamide, domperidone) are frequently observed and may contribute to such ADR. As under-reporting is a known issue in pharmacovigilance, and more specifically among PD patients, these results warrant further investigations. Causality assessments are however needed to avoid unjustified flagging."

Adverse drug reaction • Adverse events • CNS Disorders • Parkinson's Disease

"In Canada we are not using pergolide. Rotigotine has taken over!!" (@DrRana_Centrist)