Prolactin Research...

**DoctaBig** · 09-12-2004, 12:36 PM

I'm studying neuroleptic medications in my pharmacotheraputics class right now and i came across a little piece of information that intrigued me that i never thought of. Here's the low down.

Neuroleptic medications (conventional anti-psychotics (not atypicals)) work in part by antagonistic effects on DA (dopamine) receptors. There are 4 types of dopamine tracts in the CNS, here they are are with their respective general purpose:

Mesocortical - Cognition, communication, social function
Mesolimbic - Arousal, memory, Stimulus processing, Motivational Behavior
Nigrostriatal - Control of muscle movements
Tuberoinfundibular - Regulation of Prolactin release

When patients are on long term neuroleptic medication used they can have symptoms of hyperprolatinemia; this due to the drug's effect on the Tuberoinfundibular tract causing modulation of Prolactin release. When patients start exhibiting these symptoms they are put on one (or a combination of) 3 different medications: Bromocriptine, Cabergoline, or Amantadine. Those first two should seem very familiar. These drugs work by exhibiting AGONISTIC properties on dopamine receptors.

The last drug in the list, amantadine, is one that i have not heard around the boards as a potential candidate for prolactin induced gynocomastia prophylaxis and I'm curious as to why. Amantadine is very cheap (compared to cabergoline and bromocriptine) and from my current knowledge does not have any effect on androgen receptor up-regulation as B-6 does. Amantadine also has another potentially beneficial effect, It possesses antiviral properties. It is also commonly used for treating the common viral flu. Therefore it may possibly help keep the test flu away???

Keep in mind that i have only done a small amount of research so far. I have a test on Monday and a presentation on Thursday that need to be finished before i can look for studies and whatnot. I have not researched at all the toxicity associated with long term administration of the drug and/or recommended daily dosages. In the pharmacy setting i have only seen this drug prescribed short term (Viral Flu).

Does anyone have any information already on this subject, or know any reasons that it is not used during cycles to decrease prolactin levels???

**Ntpadude** · 09-12-2004, 12:58 PM

I understand that gyno requires the combination of prolactin and estrogen. One or the other alone will not necessarily cause gyno in men, just an interesting tid bit.

**DoctaBig** · 09-12-2004, 01:01 PM

that is true....but the nolva/a-dex will take care of the estrogen.

**magicstick2003** · 09-12-2004, 04:24 PM

Originally Posted by DoctaBig

I'm studying neuroleptic medications in my pharmacotheraputics class right now and i came across a little piece of information that intrigued me that i never thought of. Here's the low down.

Neuroleptic medications (conventional anti-psychotics (not atypicals)) work in part by antagonistic effects on DA (dopamine) receptors. There are 4 types of dopamine tracts in the CNS, here they are are with their respective general purpose:

Mesocortical - Cognition, communication, social function
Mesolimbic - Arousal, memory, Stimulus processing, Motivational Behavior
Nigrostriatal - Control of muscle movements
Tuberoinfundibular - Regulation of Prolactin release

When patients are on long term neuroleptic medication used they can have symptoms of hyperprolatinemia; this due to the drug's effect on the Tuberoinfundibular tract causing modulation of Prolactin release. When patients start exhibiting these symptoms they are put on one (or a combination of) 3 different medications: Bromocriptine, Cabergoline, or Amantadine. Those first two should seem very familiar. These drugs work by exhibiting AGONISTIC properties on dopamine receptors.

The last drug in the list, amantadine, is one that i have not heard around the boards as a potential candidate for prolactin induced gynocomastia prophylaxis and I'm curious as to why. Amantadine is very cheap (compared to cabergoline and bromocriptine) and from my current knowledge does not have any effect on androgen receptor up-regulation as B-6 does. Amantadine also has another potentially beneficial effect, It possesses antiviral properties. It is also commonly used for treating the common viral flu. Therefore it may possibly help keep the test flu away???

Keep in mind that i have only done a small amount of research so far. I have a test on Monday and a presentation on Thursday that need to be finished before i can look for studies and whatnot. I have not researched at all the toxicity associated with long term administration of the drug and/or recommended daily dosages. In the pharmacy setting i have only seen this drug prescribed short term (Viral Flu).

Does anyone have any information already on this subject, or know any reasons that it is not used during cycles to decrease prolactin levels???

not sure about the prevention of test flu. since techinically it isn;t a flu. just your body shutting down and thats how it is displayed.

**DoctaBig** · 09-12-2004, 04:39 PM

Originally Posted by magicstick2003

not sure about the prevention of test flu. since techinically it isn;t a flu. just your body shutting down and thats how it is displayed.

By "test flu" i meant infections due to weakened immune responce from androgen exposure. Sorry...i think that was poor word choice on my part.

**magicstick2003** · 09-12-2004, 04:43 PM

i gotcha...

**w_rballs** · 09-12-2004, 05:07 PM

ive heard about bromo, and dostinex(cabergoline) i knew there was a third one but was unaware of the name. i will have to do some reading on it, as i am very sensitive to progesterone and i take dostinex with ever cycle of fina

**DoctaBig** · 09-12-2004, 05:09 PM

post up anything on find on this thread...as soon as my week of hell is over i'll help ya out some

**Bryan2** · 09-12-2004, 08:06 PM

if you have pre existing gyno and have estrogen under control with nolva/fermara but are still getting raised prolactin level from say deca /fina something of the sort can the raised prolactin still cause breast tissue to grow even without the presence of estro?

**DoctaBig** · 09-12-2004, 08:20 PM

my answer is yes.

People get gyno from fina only and deca only cycles

i think that the two hormones potentiate each others action...

**macrophage69alpha** · 09-13-2004, 04:31 PM

something to look into.

**DoctaBig** · 09-13-2004, 08:18 PM

does anyone want to be a guinea pig once we get some more concrete info???? lol

**flexin-rph** · 09-13-2004, 08:23 PM

Hey docta...glad to see you're keeping your nose to the grindstone AND helping out
the AR scene!!! Best of luck to you!

**DoctaBig** · 09-13-2004, 08:27 PM

hehe, thanks...gotta love us smart ass pharm.D's...We're never happy!!!

**flexin-rph** · 09-13-2004, 08:54 PM

...gotta love us smart ass pharm.D's...We're never happy!!![/QUOTE]
You said it...not me!

**DoctaBig** · 09-17-2004, 08:34 PM

OK...i did some research. DocM tole me he was going help me out, so now you all know to hold him to it

Preliminarily it looks pretty promising, It appears that it will in fact work. I'm having trouble finding long term toxicity studies, but it has been used for ESPS in parkinsonian patients long-term with very few side effects. Soo thats a good sign also. If you wish to assist in the research, please by all means help out.

Anway, my college's resources suck so if anyone has good access to full text articles through pubmed i've included all the PMID #'s if by chance you have access to the full text please forward them my way.

Goods to follow:

**DoctaBig** · 09-17-2004, 08:38 PM

Management of psychotropic-induced hyperprolactinemia.
Pmid 1341991

Effect of amantadine on prolactin secretion, pituitary DNA synthesis and 3H-spiperone binding in male estrogen-treated rats.
PMID

Amantadine, a well-known antiviral agent, causing an increase in dopamine synthesis, release and the inhibition of re-uptake of noradrenaline and dopamine in central and peripheral catecholaminergic neurons, is successfully used in the treatment of Parkinson's disease. In the present paper, we have studied the effect of various doses of amantadine on in vivo prolactin secretion and the incorporation of 3H-thymidine and 3H-spiperone binding by the anterior pituitary gland of long-term diethylstilboestrol-treated male Wistar rats. Four weeks after a subcutaneous implantation of Silastic tubes containing 10 mg of diethylstilboestrol, a dramatic rise in serum prolactin levels was observed, accompanied by an increased uptake of 3H-thymidine by DNA anterior pituitary cells. Amantadine, given in the subcutaneous doses of 50, 5 and 0.5 mg/kg of body weight attenuated the stimulatory effect of stilboestrol on serum prolactin concentration in a dose-dependent fashion. On the other hand, the incorporation of 3H-thymidine into DNA pituitary cells in all the groups of amantadine-treated rats was only slightly suppressed. In an additional experiment, Scatchard analyses were performed on the in vitro 3H-spiperone binding kinetics in a dispersed anterior pituitary cell culture prepared from the pituitaries of 6-week diethylstilboestrol-treated rats. It has been found that amantadine injected in the dose of 5 mg/kg of body weight for 14 days induced a twofold decrease in the density of dopamine D2 binding sites (36.6 +/- 9.4 vs. 70.3 +/- 3.4 fmol/10(6) cells; p less than 0.02), while the apparent affinity of the receptors was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Amantadine in the treatment of neuroendocrine side effects of neuroleptics.
PMID 2884239

An open-label reversal drug study was undertaken on 10 neuroleptic-treated schizophrenic inpatients to assess the impact of amantadine hydrochloride on presumed prolactin-mediated neuroendocrine side effects. Measures were conducted across 7 weeks, including a 2-week neuroleptic baseline, a 3-week neuroleptic-plus-amantadine phase, and a 2-week return to the baseline regimen. Significant reduction with amantadine was observed on all six indices of neuroendocrine side effects: serum prolactin levels, body weight, gynecomastia/galactorrhea, breast tenderness, decreased libido, and amenorrhea. Improvement on these parameters was noted for as many as nine or all 10 patients, while in no cases was there worsening. In terms of motor and clinical effects, significant diminution of extrapyramidal and psycho-pathological symptoms was also achieved during this phase. The results suggested that amantadine may be beneficial for the treatment of neuro-endocrine side effects of antipsychotic medication owing to its ability to reverse neuroleptic-induced hyperprolactinemia.

Inhibition of plasma prolactin in the rat by amantadine
PMID 3877233
A single iv injection of 15 or 30 but not 7.5 mg/kg BW of an antiviral drug, amantadine, significantly (P less than 0.05) decreased plasma prolactin (PRL) concentrations in male rats. This effect was dose-dependent, with the highest dose producing a longer-lasting decrease in plasma PRL. The amantadine-induced decrease was unaffected by a simultaneous injection of 5-hydroxytryptophan (30 mg/kg BW) but was completely blocked by a simultaneous injection of haloperidol (0.05 mg/kg BW). It is concluded that this novel effect of amantadine on PRL is produced by an interaction with the dopaminergic system.

The effect of amantadine on prolactin levels and galactorrhea on neuroleptic-treated patients.Pmid 6117579
Amantadine was given to 11 psychotic patients, concurrently on neuroleptic medications, who required treatment of neuroleptic-induced extrapyramidal side effects. Five of the 11 patients suffered from galactorrhea, and all of these reported improvement in their galactorrhea on amantadine. Plasma prolactin levels were measured in eight of the 11 subjects, and there was a significant decrease in these levels for the group. Presumably these effects are due to amantadine's properties as a dopamine agonist and suggest a possible use of amantadine in the treatment of neuroleptic-induced galactorrhea.

Effect of trenbolone acetate on growth, blood metabolites and hormones of cull beef cows.PMID 7467111

Effects of anabolic implants of oestradiol alone or in combination with trenbolone acetate on the ultrastructure of mammary glands in female lambs regarding their interference in prolactin secretion.PMID 11913819

The side-effects of anabolic steroid implants on mammary gland ultrastructure were evaluated in female lambs treated with oestradiol (n = 10) and with oestradiol plus trenbolone acetate (n = 10). Ten non-implanted lambs were used as controls. Apart from the ultrastructural study of the mammary gland, an assessment of the prolactin pituitary cell population was carried out by immunological methods. Our results showed that oestrogenic implants exert stimulating effects on mammary gland development, both by activating the synthesis process at mammary gland cell levels and by increasing prolactin pituitary production. Nevertheless, there was no evidence of secretory products in the lumen of the gland. Implants containing trenbolone acetate counteracted the mammary stimulus of oestrogens showing ultrastructural images of cell autolysis and necrosis.

**Duke of Earl** · 09-17-2004, 08:50 PM

any thoughts on pergolide / lisuride? or selegiline?

**DoctaBig** · 09-17-2004, 08:50 PM

more good info making amantadine more tolerable

http://www.rxlist.com/cgi/generic3/cabergoline_ad.htm

Side effect - Number (percent)
Nausea 45 (27) 4 (20)
Constipation 16 (10) 0
Abdominal pain 9 (5) 1 (5)
Dyspepsia 4 (2) 0
Vomiting 4 (2) 0
Central and Peripheral Nervous System
Headache 43 (26) 5 (25)

http://www.rxlist.com/cgi/generic3/bromocriptine_ad.htm

The incidence of adverse effects is quite high (69%) but these are generally mild to moderate in degree. Therapy was discontinued in approximately 5% of patients because of adverse effects. These in decreasing order of frequency are: nausea (49%), headache (19%), dizziness (17%), fatigue (7%), lightheadedness (5%), vomiting (5%), abdominal cramps (4%), nasal congestion (3%), constipation (3%), diarrhea (3%) and drowsiness (3%). A slight hypotensive effect may accompany bromocriptine mesylate treatment

http://www.rxlist.com/cgi/generic3/amantadine_ad.htm

The adverse reactions reported most frequently at the recommended dose of amantadine (5-10%) are: nausea, dizziness (lightheadedness), and insomnia

**Duke of Earl** · 09-17-2004, 08:51 PM

actually selegiline is prob too non specific (MAO-B inhibitor)

**DoctaBig** · 09-17-2004, 09:06 PM

Originally Posted by duckman

any thoughts on pergolide / lisuride? or selegiline?

pergolide is an Erogotamine derivitive...there's a reason they aren't used anymore

from rxlist

Twenty-seven percent (27%) of approximately 1,200 patients receiving pergolide mesylate for treatment of Parkinson’s disease in premarketing clinical trials in the US and Canada discontinued treatment due to adverse events. The events most commonly causing discontinuation were related to the nervous system (15.5%), primarily hallucinations (7.8%) and confusion (1.8%).

Not for me bro....ergots are nasty stuff. I will say that i do not however know if it has any action on the Tuberoinfundibular dopamine system. I'm assuming it does, but i haven't done the research.

------------------------------------------

lisuride

also an ergotamine....which by the way is also the precursor to LSD. But this one is much closer to actual LSD than Pergolide is. I wouldn't want to hallucinate while on a tren cycle...i dunno if that is a real good idea.

------------------------------

selegiline

NO NO NO NO NO NO NO NO NO NO NO NO
Why? Selegiline is a suicide MAOI. MAOI = Mono Amine Oxidase Inhibitor. This enzyme is responsible for presynamptic breakdown of neurotransmitters. Neurotransmitters = serotonin, dopamine, nor-epinephrine, etc. Excess amounts of these is not good. These are very old drugs with MANY MANY MANY drug and food interactions. And when you screw up with these drugs its big time...hypertensive crisis leading to death if enough is ingested. Go to your local pharmacy and pick up ANYTHING on the shelf and read the drug interaction part on the label 9 out of 10 times it will say do not take with MAOI's. if that says anything

DUCKMAN are you a medical professional...those are pretty obtuse drug names to be tossing around.

**Duke of Earl** · 09-17-2004, 09:13 PM

yeah, but selegoline is a specific MAO-B inhibitor so doesn't have all the usual ''cheese reaction'' type probs ( i think MAO-B is mainly found in dopaminergic regions so you dont get all the usual peripheral sides of non specific MAO I's) ?? er ...yes...did my degree in pharmacology, but have forgotten most of it - so forgive stupid suggestions!!!

**DoctaBig** · 09-17-2004, 09:37 PM

no such thing as a stupid suggestion

. Amantadine was a lucky hit trust me, i look like an idiot every day in class. Especially when my recommendation for ADHD treatment was risperdone and mirtazapine....but I'm still standing by that one (time will tell

)

I dunno i just have a sour taste in my mouth for MAOI's though...it always seems like there is a better drug for the job???

BTW...i apologize if i insulted your intelligence. I didn't realize you had a degree in pharmacology

From a pharmacologists point of view...what do you think of this Amantadine thing??

**Duke of Earl** · 09-17-2004, 09:51 PM

I'm a bit rusty to be honest, but the studies do look promising - amantadine should be way milder ( in terms of sides ) than bromo - which for me would be the main attraction seeing as I hate bromo!

And yes - tripping on tren (lisuride) is probably a bad idea!!! - still at least when you come down you wont have tits!!

**DoctaBig** · 09-17-2004, 10:01 PM

if your not in a psych ward for attacking a old lady who you thought was hitler.

**DoctaBig** · 09-17-2004, 10:02 PM

...

....

**flexin-rph** · 09-18-2004, 05:06 AM

Originally Posted by duckman

yeah, but selegoline is a specific MAO-B inhibitor so doesn't have all the usual ''cheese reaction'' type probs ( i think MAO-B is mainly found in dopaminergic regions so you dont get all the usual peripheral sides of non specific MAO I's) ?? er ...yes...did my degree in pharmacology, but have forgotten most of it - so forgive stupid suggestions!!!

Correct. The MAOI-B drugs don't have the same reaction as the other
MAOI's (the drugs used for depression). There is no (or very little) chance for a hypertensive crisis w/ these.