How to Regain Sensitivity to PDE-5 Inhibitors (!) (Make PDE-5 Inhibitors Work Again)

UPDATE: The RS Transaderm product is no longer available (Permanently Discontinued) so as of this point we Now Recommend using the Equivalent; Dermacrine Gel and Product #17 Testosterone Booster [The "Elite" Testosterone Booster]

This article aims to parallel it's predecessor; how to regaPDEin sensitivity to nitric oxide products. Except in this case, we are specifically talking about gaining back sensitivity to PDE-5 Inhibitors - both natural and pharmaceutical. 

This includes Sildenafil (Viagra) , Tadalafil (Cialis) , Vardenafil (Levitra), Icariin, Berberine, Xanthoparmelia Scabrosa etc...

Because the above chemicals/products act to disable / inhibit the enzyme that breaks down cGMP and thus promoting vasodilation by enhancing the level of this molecule (cGMP) - the common physiological cause of losing sensitivity to these products isn't purely based on adaptive changes by chronic use...in fact, chronic use of these drugs or any -5 inhibitors should improve benefits over time...however, if you body fails to produce nitric oxide or cGMP - then there won't be much to preserve by means of PDE5 inhibitors. 

Thus, the main mechanism is to act upon the pathways that stimulate the actual production of cGMP. That way PDE-5I's may provide preservation of the cGMP already being produced.

A valuable way to do this would be to supplement with neurosteroid precursors that enhance nitric oxide synthesis and cGMP.

I recommend transdermal application of both DHEA and Pregnenolone. It's the simplest way to address any variety or degree of cGMP deficiency - without risking side-effects that may be associated with other methods.

I recommend transdermal delivery as in using something like RS Transaderm shown below - because oral DHEA and pregnenolone may be eaten up quickly by digestive acids. Simply click the image or link above to go to the product page. 

             **SOURCES / CITATIONS **

Pregnenolone sulfate restores the glutamate-nitric-oxide-cGMP pathway

Short-term dehydroepiandrosterone treatment increases platelet cGMP production in elderly male subjects.

Dehydroepiandrosterone stimulates nitric oxide release in vascular endothelial cells: evidence for a cell surface receptor.

How to Become Sensitive to Nitric Oxide Sups Again (Regain Sensitivity to N.O Products / Make N.O Products Work Again)

Alot of the nitric oxide products out there are very effective for helping to build muscle, enhance fat loss - and most of all - enhance the workout 'pump'. There are basic and advanced nitric oxide supplements, and yet, one question many people ask is "WHY do nitric oxide products lose effectiveness over time" or "why do nitric oxide products no longer work for me". 


This can occur both in those using them for workout purposes or as a sexual aide. It is an occurrence that IS very real but doesn't necessarily have to do with the product ITSELF degrading..in fact - the most common reasons for lessened responsivity  to N.O products are usually something to do with the person taking them. 

It could have to do with prescription medications that the person is taking, or it could have to do with the person using other supplements that are directly opposing the effects of the nitric oxide supplements.

Before proceeding past the other/miscellaneous factors. Please make sure that the following do not apply to you. 

• Are you taking the stomach acid blocking pills ZANTAC or TAGAMET? These pills can lower central nitric oxide production by blocking histamine receptors.
• Are you taking finasteride or other ~5alpha-reductase inhibitors~ used for hair loss or prostate enlargement? - these can cause estrogen dominance and low testosterone levels - which can negatively impact nitric oxide efficiency and production.
• Do you have low testosterone levels ?
• Do you take SSRI anti-depressants or anti-psychotic drugs?
• Do you take benzodiazepine drugs for anxiety?
• Do you take beta-blocker drugs for high blood pressure such as propanolol or bicoprolol?
• Are you using ST.John's wort, albizzia, licorice root or other natural herbs that may negatively affect endocrine function?
• Do you have a history of heart disease and / or diabetes? - both conditions are both associated and rooted in nitric oxide dysfunction.

If any of the above DO apply - talk to your doctor about making changes in your medication routine - such as 

• Switching ZANTAC or TRAGAMET for a safer stomach acid control medication such as PRILOSEC or another proton pump inhibitor. In more technical terms, switch your histamine H2 antagonist drug for a proton pump inhibitor for stomach acid control.
• Switch your blood pressure medication like a beta blocker - with an ACE inhibitor instead....ANGIOTENSIN-converting enzyme inhibitors (ACE inhibitors) have less sexual side-effects and less effects on nitric oxide production as well.
• Lower the dose of psychiatric drugs and / or switch to non-anti-glutamatergic medications - e.g switch SSRI to a dopamine reuptake inhibitor such as bupropion for depression or consider a NaSSA medication like trazodone or mianserin for depression instead. You could also use vortioxetine instead of SSRI which won't negatively affect nitric oxide production.

Now, let's get back to the OTHER MISCELLANEOUS, main cause of nitric oxide products no longer working / lessening in effect. 

The main cause of nitric oxide products no longer working is a CENTRAL NITRIC OXIDE SYNTHASE (nNOS) DEFICIENCY. 

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

Without the production of the synthase enzyme, arginine, citrulline and many other supplements will fail to convert into active nitric oxide. 

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

One of the main ways we can correct this on both a HORMONAL and enzymatic level - is by supplementing with a precursor neurosteroid supplement - these are not illegal or scheduled substances - we are talking supplements that most people overlook such as RS transaderm or PHYTOSERMS. 

The reason is because nitric oxide synthases are triggered by neurosteroids and by glutamate, which brings me to my next point.

READ THE SIGNS OF BODILY GLUTAMATE DEFICIENCY TO SEE IF IT FITS YOU

Read symptoms of NMDA-neuron deficiency to see if this is you.

If either of these paradigms fit you - read the rest of the respective article for suggestions on how to correct the molecular disturbance leading to the lack of functional response to nitric oxide boosting supplements.

What does Low Glutamate do to the Body (Signs/Symptoms of low Glutamate in Periphery/Outside of the Brain/Extremeties)

I will be making another article directly after this with a compare and contrast of mind-body symptoms. This article is meant to expand beyond just low NMDA receptor activity - and instead aims to define low glutamate symptoms within the body or in peripheral tissues/extremities.

Glutamate is the most abundant neurotransmitter in the human nervous system. It is essential to cell energy production; including the mitochondria - and is the major facilitator of both nitric oxide production as well mobilizing calcium ions, providing the vital means by which calcium is taken up by both nerve cells and non-neural sites. 



Thus, this article is essentially showing the symptoms of glutamate deficiency outside of the psychogenic responses that would be correlated with brain glutamate deficiency, and hopes to provide a separate analysis which is not fettered or disturbed by conflicting systems / reports. 

SYMPTOMS OF LOW GLUTAMATE IN THE BODY/PERIPHERY

• High Blood Pressure or Low Blood Pressure(1) (2) (3). 

** Because glutamate is necessary for nitric oxide production, low levels may lead to high blood pressure , however, a net reduction in nervous system activity may paradoxically lead to low blood pressure - thus either are possible. **

• Lack of muscle-contractions during workouts/heavy lifting.(4) (5) (!)
• Severe constipation, slowed intestinal transit, lack of bowel contractions(6)(7)(8).

** Glutamate plays a large role and is in close coordination with serotonin, especially in the gut - serotonin can trigger gut contraction and bowel movement through 5-HT4 receptors while glutamate can activate the cGMP pathway which then activates the 5-HT4 serotonin signaling pathway. Essentially this comes down to calcium-nitric oxide reactions which allow for normal bowel function.**

• Loss of appetite(9)(10)(11).

**This assertion is from both straight scientific evidence demonstrating glutamate as playing both a permissive and facilitative role in food intake, as well as demonstrated by drugs and supplements which inhibit glutamate release often producing a loss of appetite.**

• Decreased sensitivity to pain / lack of pain sensation(12)(13)(14). 
• Erectile Dysfunction (vascular and neural) (15) (16) (17)
• Muscle Weakness(18)(19).
• Loss of or weakening of taste buds/taste perception(20)(21).
• Poor respondency/no response to nitric oxide boosters / N.O products/supplements(22)(23).

** If you are asking "why do I not respond to nitric oxide boosting supplements" - low glutamate may be the reason - glutamate is necessary for nitric oxide synthesis - thus substrates and precursors such as arginine or citrulline or even PDE-5 inhibitors may not do much if glutamate is deficient.**

"How to become sensitive to nitric oxide products/boosters again"

Expanding our Understanding of IntraSocietal Fear ; Collaboration of Distrust & Neglect Fuels Conflict

Fear creates delusion, understanding that people fear hastens and allows for additional delusions, and knowing people's fears reinforces the potency and significance of that paradigm (AMx ReBorN)

Many people strive to understand, claim they understand fear, but fear persists as an entity far more sophisticated than those who have proceeded from the debut of it's vindication.

Within every portion of outward integrity, in every walking spirit - are smoldering ashes from the remainder of old feuds, traumas and distastes. Fear can re-ignite these ashes - and when one obsesses on the vibes of the past - it then can begin to form it's own life again. Memory is a powerful weapon - and an eye that never forgets , so when people see what may become of it - fear is re-inforced.

Fear has survived the times of the past and expanded it's influence to the present; but have we expanded our minds to understand fear in it's entirety? Can we predict the movement of fear and can we see it's many colors?

Fear is as much a substance as it is an emotion, but it is an emotional substance; flourishing with almost electrical current and making up the collages of people's esteemed presentations. Whether at 10% or 90, fear defines personality, or rejects it. Fear is owed a crown that many fail to appreciate, and yet, when it is undeserving, people appreciate it too much.

Fear largely takes on two forms.

1.) A vessel of reflection.

2.) As a relay of imperfections.

Yet, one can argue the two points are the same, but can we elaborate on the invigorating posture of fear as it self-molds itself into either of the above? Moreover, can we suppress the destructive influence of fear in either form?

Fear is also a currency of communication - one that often partakes in the ostracism of invalidities and unfit entities.  It becomes a reference point deemed worthy to be utilized for the sake of what is called "the better purpose" - and a shining sword for those who practice deceit. Fear is a facilitater of fraud and contempt, and a mainstream forgery peaked by the shallowness of society. 

Now when fear creates delusion, it heckles the heckled - fear becomes a whirlwind that resides with the stressor while amplifying it. 

              HOW FEAR CREATES DELUSION -                    EXPANDING ON THE BELOW QUOTE

Fear creates delusion, understanding that people fear hastens and allows for additional delusions, and knowing people's fears reinforces the potency and significance of that paradigm (AMx ReBorN)

Further than this, my belief has led me to the observation that wherever there is fear, there is also mercy. Because often through fear, our greatest progress is yet made by retention. When we are in fear or a cold sweaty panic, or engulfed with ruminations, we may certainly feel at a loss. Like we are at a disadvantage. The reality is, during these times our strongest character is built. We become steadily immune to what we have faced, and even if not right away - it leads us to action and resolve. When we win this war - when no longer is fear able to consume us, (and not because we are FearLESS) - then we admit to ourselves our greatest insights and indignations. 

Now we build character. 

Fear is something that certainly can be paralyzing, but in the midst of our struggles we must realize that we are merely looking through an alternative mirror. A cloudy one.

One that does not last against us because when our eyes really open, we see beyond those clouds. Beyond the shroud of darkness. 

This is the signature of fear-adaptation, and of strength, and of courage. 

Mercy is there when we call for it - but even if not directly superseding the state of panic; it remains readied when we may apply. If nothing else, then mercy is a powerful substance that rectifies the situation afterwards...and the gloom and painful memories are replaced by being above these fears. By adapting to , and controlling them. By rising above the madness.

It is then we become perfect examples of humanity - and of what human life teaches the world. It distinguishes us from simpler mammals -
and shows us how brilliant, we all really are!!!

ON THE FLIP SIDE 

With with regard to 'legal' code and expectations by 'society' - we are often thrown a double-negative. We often wonder what makes some of those who ignore what is 'politically correct' as dubious as those who struggle to fit in the motto. Then when we question the stigma's of society outwardly, when in fear - we are often criticized and even humiliated.

"Oh well If I do this I'll be looked at like this or as this"

This is the problem with humanity and our "process of resolve"; you will never truly make it anywhere above the median if you think that way...seriously, who the hell cares - you make yourselves look more suspicious and idiotic when fear rises to the surface to justify what others call 'logic'. The LAW is NOT God and many of our laws are not even biblical !

Hence in any sort of objective you aim to complete 'within the lines' - it becomes only so unfruitful as the rest of the fools who scrub floors for free! 

Society is 'branding' people with a plethora of ridiculous stereotypes and yet the ones who disregard the possibilities often end up 'not being labeled' ....simply because we look suspicious or weak by being so conscious of society's standards. FEAR as powerful as it can be is often just a 'state of mind' that wreaks havoc on mental clarity and so I assure you - you can get away with more than you think by being less prudent and more disregarding of societies petty little headlines. 

If you want to truly take on a respectable form - you must have a near perfect balance between fear and logic; and most of the time - this is when fear is at 10-20% and not enough to 'lock' us into a pervasive but tempered 'fight or flight' response. 

You want to win in life - or perhaps get away with a bunch of 'unfavorable' or controversial acts ? Stop attesting your bravery and mind yourself - if you no longer become so mindful of labels then you have now the clarity to bypass simple error's in human perception. 

As such, you can re-program your mind to extinguish fear consolidation and / or simply dismiss fears by operating on your own standards . 

However, there is a degree of acceptability necessary to climb the latter.

So of course, it's about how you carry yourself - and especially about timing and analysis.

Put on a facade if necessary but maintain your INTEGRITY. 

You can't be labeled if you are clear-headed and even if you are ; there's ways out of it without political or collaborated anti-sabotage efforts.

Oh..so the guy who's 240 lbs and has to wear a skull and crossbones shirt should probably 're-advise' themselves on their torture porn connoisseur-ism and hide the shit in an encrypted file! Some people just don't 'have it' or seemingly aren't meant to get away with stuff...and again, usually because of a lack of flexibility...or you could argue about some 30 year old guy dating a 16 year old girl...as ridiculous as it sounds - there are ways to get away with it by disregarding societal standards, maintaining vigilance and most of all - being ' clean' and not leaving ' evidence ' behind. Additionally, if you are a hacker you can simply look up details of who they are / their family etc...

Then its just about personality alignment and veering in a fairly clean direction and also how much is exposed..but if you look like a zombie and rugged it will probably make it harder to get away with such things..so I s'pose you still need a little 'fear' but as far as being labeled for such things - laugh at the concept of it (perhaps to yourself) and drift thy feeling into the abyss as if it doesn't exist... !


Political criminals and other perverted high-figures get away with it because they do not allow the thoughts and opinions of others to 'stab deep'; avoidance strategies are re-structured to look appreciable and under a new guise. One right action therefore can masquerade a thousand dark actions...and this is how political corruption comes along. 

Divert, DIVERT, DIVERT - if you hide your true intentions it's possible to get away with anything. 

Does this mean I agree with malicious intent or unscrupulous actions? No. It truly is about sending a message. So to the same by politicians and bankers who own most of the worlds power and resources - you see...because I'm simply showing you both the positives and negatives of fear - fear and anxiety not necessarily being the same thing but often co-ocurring. 

EVER STOP TO WONDER WHY Some Retail employee's get shot at a hold-up or bankers get shot during a robbery?

FEAR AND PARANOIA

"I don't want to run the risk of being identified so I'll kill them as an 'insurance policy'.

So interestingly, fear often appears to others as fearlessness or  a lack of conscience. Fear often leads to the darkest acts and as such is present as a tool within AND by various criminal organizations... it is logical though, from their perspective, isn't it?

So therein lies the point - both too much fear and a complete lack of fear both = weakness and blindness.

But it is dependent on the situation and so interactions must be thoroughly analyzed whilst not causing yourself anxiety - and trust me..not many people have the necessary combination of patience and vigilance - paranoia is often seen as 'manic' and indeed....it does us no good in such a neurotic form..only when stabilized and allocated as a computer would then perform necessary security swipe without compromising speed and efficiency...do you understand now?

Fear and fearlessness are one in the same - you just have to understand them both better than what most want you to or are too ignorant to understand themselves...

Can Serotonin Cause High Blood Pressure / Hypertension ? (Serotonin causing High Blood Pressure)

Despite all of the erroneous marketing and exaggerated claims regarding SSRI's - serotonin is not some God-Tier-powerful substance that can eliminate all of our health problems. While deficient states can certainly lead to constipation or other bowel disorders (1), excesses can be just as harmful with that paradigm of disorders and even more harmful systemically(2). 

Additionally, it's unclear whether low serotonin itself actually causes any abnormal mental state , as there is mixed evidence with much of it showing that antagonizing (blocking) certain serotonin receptors is a more valuable strategy for treating psychiatric disorders. { ! } { ! }


Serotonin is implicated in a number of cross-reactions in the nervous system, and there are serotonin receptors located directly in/on the heart/atrium. Increased activity of the serotonin receptors 5-HT2B and 5-HT4 is shown on failing hearts. (3) (4)

As such , chemicals/drugs that block these two serotonin receptors are being investigated/trialed for the treatment of those with various forms of heart disease. (5) (6)
Namely, right ventrical heart failure (5-HT2B) and congestive heart failure (CHF) along with tachycardia (5-HT4).

In addition to central heart failure, serotonin itself is dangerous in moderately-elevated to substantially elevated amounts, high plasma serotonin levels are found to cause primary pulmonary hypertension (7) (8) (9).

Additionally, serotonin is found to , along with adrenaline, mediate stress-induced increases in systolic blood pressure, which essentially means that serotonin is about half of the reason why blood pressure can go up in response to stress(10) (11).  Part of this has to do with the serotonin induced accumulation of ALDOSTERONE via 5-HT4 receptor activation(12).

This means that serotonin allows for sodium retention as well as excessive calcium ion influx via that receptor.

Finally, anabolic steroid use, especially that of nandrolone or progestin based steroids - leads to the (abnormal) downregulation of serotonin autoreceptors which then may lead to the direct enhancement of serotonin signaling at the 5-HT4 receptors - which may be a valid hypothesis or at the least, a contribution by AAS in heart failure/enlargement(13) (14) (15).

IN CONCLUSION

• Serotonin can certainly cause hypertension; high blood pressure in young and old if it is elevated in an abnormal fashion or is consistently elevated above the median.
• Increased serotonin over time can leading to a failing heart and increased 5-HT4 receptor activity seems to be a valid hypothesis for anabolic steroid induced hypertrophy of human atrium .

................

Work in progress.

What Chemical/s, Drugs, Supplements can Produce Euphoria and yet Decrease Libido?

This question will mark the beginning of a set of 10 questions e-mailed to me, I am picking 10 worthy questions ., hard Scientific questions that do not have a very simple answer, at least to most people.

How can one produce euphoria and other symptoms of high dopamine, including high dopamine itself and yet reduce libido?




There are two main main ways this can be done.


1.) Use of narcotics of the opiate class, specifically those with a high blood brain barrier penetration - those with psychotropic properties...the reason for this is opiates can raise dopamine in behavior related areas while antagonizing it or generally diminishing activity in the areas concerned with governing sexual behavior. 

Opiates can increase dopamine receptor expression and also have a diverse effect on serotonin whilst lowering acetylcholine levels - this leads to a trance-like-euphoric state at the right dose, but due to inhibition of sexual circuitry, it usually goes along with a decreased libido.

This is also due to oxytocin antagonism by opiate drugs and the inhibition of glutamate neurons necessary to express a normal libido.

• -One may be euphoric, but un-empathic.
• -It is not a tactical euphoria, but a self-centered one.
• -It has some parallel's to LSD, but many differences and less chance of hallucinations.

2.)  Use of NMDA-receptor antagonists.

Such as memantine (Namenda XR etc) or ketamine and other similar tranquilizers. 
These can produce euphoria and / or grandiosity but they can also produce psychotic symptoms. It is a transient euphoria, but less energy rigging than opiate related euphoria.

How to Prevent/Reverse Dopamine Receptor Downregulation from Dopamine Agonists, Stimulants and other Causes

While it is certainly notable that many neurodegenerative diseases can cause malfunction in dopamine neurons (Parkinson's, MS, Infections, FMNP, CFS) - that doesn't mean that dopamine issues can not occur without their involvement...and organic and / or idiopathic (of unknown cause) dopamine deficiency is not the only form of imbalance nor does it always affect receptor expression and / or internalization.

There's also drug-induced downregulation - a problem encountered often in scientific study and sometimes in mental patients taking specific Psychiatric medications. Some antibiotics may influence receptor expression as well.

ADHD sufferer's who take Ritalin should be made aware that their medication may decrease in effectiveness over time - in part due to downregulation of dopamine receptors as well as increase in dopamine transporter activity...

Parkinson's patients on dopamine agonist drugs may experience a lessening in effects/benefits after the period of 3-6 months - an effect that can also be prevented and / or reversed by the below methods.


My only main recommendation to both prevent and reverse downregulation is one backed up by clear scientific study. 

A stack consisting of ...

(NOTE: You only have to use 2 or 3 out of these but you CAN use all five if you wish, it might be a bit overkill though.)

1.) Phenyl Piracetam 
 This is a racetam derivative / analogue that has the unique ability to increase dopamine D1, D2, D3 expression and to protect dopaminergic neurons(1) (2). It has nootropic effects , thus improving cognitive/brain function and can be bought over the counter.

HOW TO TAKE IT: Take 100mg 2-3 times a day, dose the latest dose at evening time no later than 6 PM. Take for at least 3-6 months during or post-treatment.

Can be purchased here --> http://www.ceretropic.com/phenylpiracetam-hydrazide/
                                           

2.) Tianeptine
Use with caution and start with low doses, tianeptine is a serotonin modulating and dopamine enhancing anti-depressant/nootropic with a strong safety record and low remission rate (3). Tianeptine can improve anxiety and depression while boosting dopamine receptor concentration(4).


HOW TO TAKE IT : Take it at dosage of 12 mg THREE TIMES A DAY. Do this for 3-6 months, ideally..although as with phenyl piracetam, you will notice benefits within the first weeks - peak effects and such occur later. 

It can be purchased at Ceretropic over the counter --> http://www.ceretropic.com/tianeptine-sulfate-powder/ 



3.) LAVENDER ESSENTIAL OIL / EXTRACT

Usage of lavender has been shown to also increase dopamine receptor concentration (5) and to help alleviate stress - it is one of the most powerful natural anti-anxiety remedies available..it also has benefits in those with OCD; Obsessive-Compulsive-Disorder(6).

I recommend the 'Young Living' Lavender essential oil. {CLICK HERE}
                                                   

4.) Inositol 
Inositol is shown to increase STRIATAL dopamine D(2) receptor concentration specifically. 
Must be used continuously(7)
I recommend Solgar brand. {CLICK HERE}

                                                     


5.FORSKOLIN 
Forskolin raises HUMAN DOPAMINE D(2)L receptors and also promotes nitric oxide activity. THIS ONE is especially good for increasing libido / arousal and for enhancing the WORK OUT PUMP! (8) (9)
Forskolin is studied in potential erectile dysfunction treatments. (10)

I recommend Analyzed Supplements 'Forskolin-95'
Click the word or the image below to go to the Product Page.

How to Counter-Act Side-Effects of Dopamine Agonist Drugs (Safe, Cited)

Much of the reason for occurrence of side-effects in those taking the anti-parkinsonian drugs in the dopamine-agonist class ; is either the A.) polypharmacological effects and / or unspecified actions of the drug in question, or B.) paradoxically, the selectivity of the drug to only occupy the dopamine D2 class of receptors and thus causing too much cAMP reduction.

However, there are some other factors...

I will speak of specific side-effects and how to counter-act them efficiently, and safely.
You will need to evaluate these methods with your physician and also weigh them in your current situation and with other factors such as your age, blood pressure etc

Doing so will ensure a clean counteraction, without diminishing beneficial properties of the drug etc.

1.) Sedation, somnolence and / or fatigue ; Dopamine agonists seem to upregulate, and the general, persistent activation of D2 receptors seems to also upregulate, the MU-OPIOID (MOR) receptors (1) (2) - which leads to inhibition of CNS activity; GABA alteration(3), acetylcholine(4) inhibition  partly mediate this effect and result in respiratory depression as well as fatigue. Therefore, a mild-moderate mu antagonist may alleviate these unfavorable effects, but may also delay the onset of sleep, and thus should only be taken advantage of during the day.

A simple solution is often overlooked, simply drink Coffee during the day, coffee in it's whole form, either instantized or ground and brewed contains mu-opioid antagonist compounds - CAFFEINE is NOT the chemical responsible for this effect, but rather other chemicals found in the bean / in coffee. <see citation here>   
               <second source>

You can also use forskolin during the day , or in severe cases, forskolin plus coffee, however, forskolin should be used with caution if on high blood pressure medication(!) (!) (!).

Your doctor should be fully aware of the interaction with dopamine agonists and opioid analgesics, dopamine agonist drugs should not be used with opiate narcotics or used with extreme caution and careful dose titration.

2.) Constipation. (less common than diarrhea)
This also seems to be related to the mu upregulation and also can be counter-acted by drinking coffee(4)(5), however, it could also be related to the reduction in Adenylate Cyclase caused by dopamine agonist drugs - an alternative method besides only coffee consumption is to add FORSKOLIN - which activates adenylate cyclase....because dopamine receptors possess OTHER PROPERTIES besides being negatively coupled to G-Proteins, they do other things besides adenylate cyclase inhibition..using forskolin will  NOT diminish the beneficial effects of dopamine agonists -  in fact, it may enhance the beneficial effects ...however, forskolin should be used with caution in those on blood pressure medication.



3.)Paradoxical reduction in libido. 

Some have reported decreased libido on dopamine agonists, normally, these drugs increase sex drive, but in those that it does the opposite - it probably is due to an over-inhibition of cAMP and / or an overlooked predisposition such as estrogen dominance.

In which case, look for estrogen issues in blood work - if it is high, then using an aromatase inhibitor will be necessary...if it is low - using D-Aspartic acid with your dopamine agonist will help. If no estrogen imbalance exists..then it is probably due to cyclic AMP reduction, in which case...forskolin addition to your dopamine agonist should alleviate the issue.

Effect of a dopamine agonist on luteinizing hormone receptors, cyclic AMP production and steroidogenesis in rat Leydig cells.

D2-dopamine agonists inhibit adenosine 3':5'-cyclic monophosphate (cAMP) production in human term trophoblastic cells.

4.)  NAUSEA :: Nausea is probably the most common side effect of dopamine agonist drugs, but can be counter-acted easily...though the effects may be prominent and / or annoying, fret not, using high-dose ginger capsules along with ginkgo biloba daily can easily counter act this effect. Use ginger and ginkgo twice a day. Ginger can be taken at night as well.

You can also ask your doc for medications. Some anti-nausea drugs can potentially block the benefits of dopamine agonists - however, there are two exceptions...serotonin antagonists; TROPISETRON and ONDANSETRON(Zofran)

AGOMELATINE - A Powerful Anti-Depressant that Alleviates Insomnia, Balances Circadian Rhythms and Enhances Dopamine Activity

This article has been exclusively written for TrueLIFE Research - TeamTLR.com and to foster further progress within serotonergic neuron research and in establishing a basis for legitimate research with the viable compound  AGOMELATINE. 

----------------AGOMELATINE can be purchased of 99%  PURITY @TeamTLR below---------------------

http://teamtlr.com/sleep-promotion-research/44-agomelatine-99.html

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Agomelatine is a novel and extremely valuable addition to the anti-depressant class of drugs. Agomelatine has a superior safety profile and very 'clean' mechanism of action.

It is a  melatonin receptor agonist (MT1 (Ki=0.1nM) and MT2 (Ki=0.12nM)) and a 5-HT2C (Ki=631nM) receptor antagonist.[1]

It is highly efficacious at the target dose of 25mg, but it is often well-tolerated for more depressed or sleep deprived individuals at the dosage of 50 mg[2].
Agomelatine has shown improvements in both youthful [3] and elderly patients[4] [5], and has the added benefit of normalizing sleep cycles / circadian rhythms[6]. A pooled analysis and four randomized clinical trials state that agomelatine is better tolerated overall than SSRI's [7] and another study shows that it does not cause sexual side-effects[8]. It is thus seen as an age-friendly, characteristically safe anti-depressant on multiple levels with a very balanced effect.


         SPECIFIC BENEFITS AND ELABORATION ON MECHANISM OF ACTION


Agomelatine is specifically a melatonergic agonist[9], that means it essentially acts at specific melatonin receptors and thus balances the sleep-wake cycle...perpetuating the ability to sleep at night and waking up refreshed. Because of this property, it can improve neurological and hormonal parameter's and improve depression and occurrences of some forms of anxiety resultant from deficits in sleep or inverted circadian cycles[10]. 

Agomelatine is additionally a serotonin 2C antagonist[11], this essentially will lessen/inhibit the ability of serotonin to interact with that receptor and as a result - the constitutive activity is lessened from. When antagonized, dopamine release is provoked due to signal disinhibition. This essentially means that agomelatine can raise dopamine levels and can improve quality of life. It is reported to significantly improve anhedonia that is caused by SSRI's and other serotonergic agents as well as anhedonia from other causes[12][13][14].


Norepinephrine may also be disinhibited by this mode of action, which can theoretically improve sensory arousal deficits; such as decreased sense of smell, vigilance and hearing. It may improve perception of quality of life and general energy levels[15].

By modulating the above neurotransmitters, this agent can be very effective in providing a comprehensive attack on depression and anxiety. But most importantly, it has become an extremely novel and important agent in the research of circadian rhythms and the treatment of sleep-wake disorders of various etiology. As we have gone past a "glance" at melatonin's involvement, and instead moved to the next phase in clinical settings - quality of life can improve, and the future is charted for further developments that may be groundbreaking in sleep studies and disorders[16][17].