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New Information on Mechanism of Action of Pergolide


Eleanor Kellon, VMD
 

It has been established that PPID is caused by decreased production of dopamine by neurons in the hypothalamus which normally keep activity of the intermediate pituitary lobe in check. We talk about pergolide working because it is a dopamine agonist which stimulates D1 and D2 dopamine receptors, in essence substituting for the lost dopamine. A new study [October 2020] from Michigan State has proven there is more to it than that.

Research looking at the levels of dopamine in the pituitary of aged, young and treated (1 mg pergolide per 500 kg for 6 months) vs untreated PPID horses has found levels of dopamine in the pituitary are actually increased by pergolide.  The activity of tyrosine hydroxylate enzyme, which generates dopamine from tyrosine, was also increased in the hypothalamus.

Based on data from other species, the researchers hypothesized that pergolide  allowed dopamine to reaccumulate in dopamineric neurons by decreasing the demand for it - substituting for some of the natural dopamine. Activating the D1 and D2 receptors may also provide positive feedback to the remaining neurons, resulting in increased tyrosine hydroxylase activity.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517620/
--
Eleanor in PA

www.drkellon.com 
EC Owner 2001


cusslady
 

Thank you for the link.  I teach veterinary pharmacy, so I appreciate seeing the latest peer-reviewed studies.


On Sun, Oct 25, 2020 at 12:44 PM Eleanor Kellon, VMD <drkellon@...> wrote:
It has been established that PPID is caused by decreased production of dopamine by neurons in the hypothalamus which normally keep activity of the intermediate pituitary lobe in check. We talk about pergolide working because it is a dopamine agonist which stimulates D1 and D2 dopamine receptors, in essence substituting for the lost dopamine. A new study [October 2020] from Michigan State has proven there is more to it than that.

Research looking at the levels of dopamine in the pituitary of aged, young and treated (1 mg pergolide per 500 kg for 6 months) vs untreated PPID horses has found levels of dopamine in the pituitary are actually increased by pergolide.  The activity of tyrosine hydroxylate enzyme, which generates dopamine from tyrosine, was also increased in the hypothalamus.

Based on data from other species, the researchers hypothesized that pergolide  allowed dopamine to reaccumulate in dopamineric neurons by decreasing the demand for it - substituting for some of the natural dopamine. Activating the D1 and D2 receptors may also provide positive feedback to the remaining neurons, resulting in increased tyrosine hydroxylase activity.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517620/
--
Eleanor in PA

www.drkellon.com 
EC Owner 2001



--
Susan E. Robinson, Ph.D.
Professor of Pharmacology and Toxicology, retired
Virginia Commonwealth University
512-436-9388 (home)
512-552-0820 (cell)


celestinefarm
 

Dr. Kellon,
Thank you for the article. Great information , especially for those whose horses have mild symptoms and not "out of normal" test results and are wondering if they should start pergolide.  Does the average protein intake of horses on forage accomodate enough tyrosine to not warrant supplementation of additional tyrosine or a generalized protein supplement?

--
Dawn Wagstaff and Tipperary   

Saline, MI  2003

Tipperary Case History

Juniper Case history: https://ecir.groups.io/g/CaseHistory/files/Dawn%20and%20Juniper/Case%20history%20Juniper.pdf .


 

Fascinating! You would think that would reduce or slow down neuronal apoptosis (neuronal cell death). If the neuron is able to produce and store dopamine even at a slower rate, vs. being exhausted by the demand, you would think the cell would be less stressed and live longer - thinking of the mitochondrial energy demand to remain a functional neuron. That may also partly explain the significantly longer life span of treated vs. untreated PPID.
--

Kathleen (KFG in KCMO)

Director and Research Advisor, ECIR Group Inc.

Missouri, USA, 2005

https://scholar.google.com/citations?hl=en&user=3-I7UI0AAAAJ 

 


Frances C.
 

Dear Dr. K, all this is too much for my feeble brain. Do we want to increase Dopamine? Would it be appropriate to feed L-theanine, a derivitive of green tea? I have been giving 1/2 teaspoon per day.

----- Original Message -----
From: Eleanor Kellon, VMD <drkellon@...>
To: main@ECIR.groups.io
Sent: Sun, 25 Oct 2020 13:44:20 -0400 (EDT)
Subject: [Special] [ECIR] New Information on Mechanism of Action of Pergolide

It has been established that PPID is caused by decreased production of dopamine by neurons in the hypothalamus which normally keep activity of the intermediate pituitary lobe in check. We talk about pergolide working because it is a dopamine agonist which stimulates D1 and D2 dopamine receptors, in essence substituting for the lost dopamine. A new study [October 2020] from Michigan State has proven there is more to it than that.

Research looking at the levels of dopamine in the pituitary of aged, young and treated (1 mg pergolide per 500 kg for 6 months) vs untreated PPID horses has found levels of dopamine in the pituitary are actually increased by pergolide.  The activity of tyrosine hydroxylate enzyme, which generates dopamine from tyrosine, was also increased in the hypothalamus.

Based on data from other species, the researchers hypothesized that pergolide  allowed dopamine to reaccumulate in dopamineric neurons by decreasing the demand for it - substituting for some of the natural dopamine. Activating the D1 and D2 receptors may also provide positive feedback to the remaining neurons, resulting in increased tyrosine hydroxylase activity.

www.drkellon.com 
EC Owner 2001




--
- Frances C.
December 2017, Washington & California
Case history: https://ecir.groups.io/g/CaseHistory/files/Frances%20and%20Phoenix
Phoenix's Photo Album: https://ecir.groups.io/g/CaseHistory/album?id=12382


LJ Friedman
 

Based on this information, are we being asked to do anything differently in managing our horses?
--
LJ Friedman  Nov 2014 Vista,   Northern  San Diego, CA

Jesse and majestic ‘s Case History 
Jesse's Photos

 


Eleanor Kellon, VMD
 

We don't know actual requirements but tyrosine is nonessential meaning it can be synthesized (from phenylalanine). No tyrosine deficiency has been identified and there are good amounts in forage - both tyrosine and phenylalanine.
--
Eleanor in PA

www.drkellon.com 
EC Owner 2001


Eleanor Kellon, VMD
 

Good point, Kathleen.
--
Eleanor in PA

www.drkellon.com 
EC Owner 2001


Eleanor Kellon, VMD
 

Francis,

PPID is caused by insufficient dopamine. Pergolide substitutes for it and this new information shows it also increases dopamine. L-theanine isn't involved.
--
Eleanor in PA

www.drkellon.com 
EC Owner 2001


Eleanor Kellon, VMD
 

LJ,

No, nothing different.
--
Eleanor in PA

www.drkellon.com 
EC Owner 2001