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Sunday, January 31, 2016

The NeuroPharmacology of Copper (Copper and Neurotransmitters / Release) Copper Mechanism of Action in the Brain



Copper (Cu) is an essential trace mineral and common metal whose ions permeate the blood-brain-barrier and exert multiple actions on receptors and brain proteins...

  • Copper (Cu) acts to noncompetitively inhibit/antagonize/block NMDA-Glutamate Receptor Currents. (1)
  • Copper plays a primary role along with Ascorbic Acid in converting Dopamine --> Norepinephrine. (2)
  • Copper stimulates the Adrenal Gland's. (3)
  • Copper augments Acetylcholine activity. (4)

Copper-dependent regulation of NMDA receptors by cellular prion protein: implications for neurodegenerative disorders

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382327/

Copper deficiency alters rat dopamine beta-monooxygenase mRNA and activity.

http://www.ncbi.nlm.nih.gov/pubmed/10573542

Effect of antipsychotic drugs on the gene expression of NMDA receptor subunits in rats.

http://www.ncbi.nlm.nih.gov/pubmed/9051657


Role of copper in human neurological disorders


http://ajcn.nutrition.org/content/88/3/855S.full

  • Copper and Copper Proteins in Parkinson's Disease

  1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941957/

Effect of ascorbic acid administration on copper-induced changes of rat brain hypothalamic catecholamine contents.

http://www.ncbi.nlm.nih.gov/pubmed/3407385


Analysis of Copper and Zinc Plasma Concentration and the Efficacy of Zinc Therapy in Individuals with Asperger’s Syndrome, Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) and Autism


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235993/

Effect of dietary copper deficiency on the distribution of dopamine and norepinephrine in mice and rats.


http://www.ncbi.nlm.nih.gov/pubmed/15539197

Copper modulation of NMDA responses in mouse and rat cultured hippocampal neurons.

http://www.ncbi.nlm.nih.gov/pubmed/8950090

Pro's and Con's of Using Naltrexone to Treat Male Sexual Dysfunction (A Broad View on a Difficult Question)




Naltrexone may very well be, one of the most effective substances for male-sexual enhancement and dysfunctions; when used Properly.

Even though, this is not the intent nor medical application of the drug, under most circumstances, it has been studied in the context of both opiate-induced-impotence and in fairly large studies of Men with idiopathic Impotence (E.D with Unknown Aetiology) (1) (2).

Naltrexone also increases 'intensity of arousal' and orgasm frequency (3).

In Healthy, normal Men even, there is a reported in enhancement in sexual functioning (4) (5)

Additionally, it has anti-aging benefits and anti-stress benefits (6) (7).

A Couple Initial . Notes before we get into the deeper discussion...
  • In any case, Naltrexone for sexual improvement should be used at a MINIMUM of 12.5 ((MG)) but PREFERABLY 25 - 50 mg ONCE / per day or 25mg TWICE/ day.
  • It can not, should not be used with Modafanil or Yohimbine under any circumstances; and Caffeine intake should be low as possible until a further assessment of Tolerance/Sensitivity is committed to.

NOW, to the big picture.

PRO's of Using Naltrexone to treat Male Sexual Dysfunctions / Erectile Difficulties

  • It seems to help with the libido component, more than other 'medically recommended' chemicals.
  • It supports dopamine production through indirect pathways as well as other neurotransmitter systems like glutamate and nitric oxide (N.O/nNOS) (!) (!!)
  • It affects orgasm quality and frequency whereas other drugs such as Viagra & Cialis seem not to.
  • It has tons of other benefits not limited to; anti-aging, stress issues, memory dysfunctions/cognitive flexibility issues and some Psychiatric disorders.

CON/S NEGATIVE'S
  • Naltrexone may produce Anxiety in some individuals as it produces mild nervous system stimulation.
  • Naltrexone may dramatically alter sensitivity to Stimulant's (!!!).
  • Naltrexone alter's sensitivity to Alcohol (!!!!).
  • It probably won't help an issue caused by heavy drinking or serotoninergic drugs.
  • It will not ''cure'' a dopamine deficiency nor a prolactin excess.
  • It will not help much, if at all, if the issue stems from E2 Excess; estrogen excess (high levels of the female hormone).
  • It may have more side-effects if you are overweight.
  • It can produce a small increase in heart rate.
  • The Pills taste nasty.





IS NALTREXONE HEPATOTOXIC / DOES IT RAISE LIVER ENZYMES?

The Answer to both Questions is No.

Click ~IMAGE~ Below.











Saturday, January 30, 2016

What Determines 5-HT5A Receptor Expression? (How to Regulate 5-HT5A Receptors)


Previously, I had elaborated on how ''mysterious'' the human serotonin 5-HT(5)A Receptor is. In Particular, how it's role as a GPCR (G-Protein Coupled Receptor) results in the relative decrease of the vital second messenger cyclic AMP (cAMP) (1), an effect that normally, would result in Reduction of some forms of nervous system stimulation, yet, despite reducing calcium mobilization - it plays a Primarily anxiogenic role (2) (3) (4); including in LSD's not-so-pleasant effects (5) (6) (7)



  1. This means that, activation of the 5-HT5A Receptor , seems to reduce N-Type Calcium Channels as a direct consequence of it's actions on G-Protein's (reducing cAMP) (8).
  2. Yet, it , when activated, increases Anxiety-like behavior - especially ''STARTLE'' resultant from sudden noises and changes in environment (9) (10).
  3. If one is too sensitive to environmental cues and projections - one is less likely to become social and outgoing; veering into the direction of social aversion is consistent with human studies linking alterations in this receptor to Schizophrenia and Depression / BiPolar (11) (12) (13) (14).


With all of this being taken into Account - it makes perfect sense to find ways to downregulate the 5-HT5A Receptor ; a receptor I am officially coding as the ''Receptor of Exploration"...for reasons I will get into More later in this Post....



  • In Regards to ANXIETY, 5-HT5A Receptors act as ~AutoReceptors~ that inhibit/decrease Serotonin release in key Area's of the Brain (15).
  • They also appear co-localized with GABAergic neurons; leading to a decrease in GABAergic transmission when activated (16) (17).
  • 5-HT5A Receptors affect exploratory behavior on multiple levels - by SMELL, SIGHT, HEARING...imagine the Euphoria of entering into a new Country, or being in a Cave or Mountain somewhere - well, the 5-HT5A Receptor ''regulates'' the processing of these smells as well as the retention of associated visual cues...too much 5-HT5A Activation creates an internally preoccupied state which leads to reduced capacity for cognitive flexibility and psychotic-like features - thus, we are no longer interested in novel environments and smells , and a Zest for traveling or moving, really, at all, disappears...thus providing a role in 5-HT5A-mediated-anxiety-Induced Anhedonia... (18) (19) (20)...

NOW..HOW ON EARTH DO WE REGULATE THIS ODD, RECEPTOR...

  • Oddly enough, LEPTIN seems to influence 5-HT5A Expression; specifically, the administration of which - DECREASES 5-HT5A in the Hippocampus (21), so there's something.
  • Estrogen; the female sex hormone - decreases 5-HT5A Receptors in the Hippocampus but increases them in the Pituitary (22) (23).

The answer is in the Puzzle itself - if we can control the amount of Leptin we might have a viable way to methodically 'deregulate' the 5-HT5A Receptors...

  • We'd have to increase the APPETITE-SUPPRESSING-HORMONE LEPTIN (Satiety-Producing).
  • Increase Free Testosterone (FT/FTT) to ALLOW for *some* Brain Estrogen to reduce the concentrate of the 5-HT5A Receptors in Memory-Related-Brain-Region/s (Hippocampus).

IT REALLY IS THAT EASY..

  1. Try L-Histidine + Folate; histamine is shown to both increase leptin levels and accelerate the response to Leptin - especially in the HYPOTHALAMUS; where it COUNTS (24) (25) (26) (27).
  2. A Free Testosterone booster like Tongkat Ali WITHOUT an Anti-Estrogen may help facilitate the effects noted - but ONLY if you use the 1st Method as Well!!




**OTHER NOTES**
  • 5-HT(5)A Receptor is HEAVILY Involved in Serotonin's REDUCTION In Sensory Activation; Skin/Thermal ETC... (1) (2) (3)
  • 5-HT5A Receptors may Play a larger Role in Endocrine Activity than Just Vasopressin/Oxytocin Modulation... (4)
  • VALERIAN EXTRACT Acts as a ((Partial Agonist)) at The Receptor. <see here>



Saturday, January 23, 2016

How to Stop Zinc From Inhibiting / Blocking the NMDA Receptor/s



One of the hardest and most festering dilemma's is potentiating/increasing NMDAR function/integrity , so in order to (or in hopes of) increasing LTP (Long-Term-Potentiation) and Synaptic Plasticity. The NMDA (N-Methyl-D-Aspartate) Receptor is an Ionic Glutamate Receptor (1) which can be activated by several ligands/amino acids..such as Aspartic Acid, Glutamic Acid, Glycine and D-Serine (2) (3)

However, it's function is dependent on how much of a 'block' or interference there is from other molecule's; notably the Zinc (Zn2+) and Magnesium (Mg2+) ions (4) (5). Magnesium blockade of the NMDA receptor complex can be easily removed without stopping the majority of Magnesium's benefits by using the memory enhancing drug NEFIRACETAM (6).

Until now , however, there has been no clear way to actually reduce or eliminate the Zinc (Zn2+) inhibition of the NMDAR. Tyrosine Kinase Src is a non-receptor protein complex that , when activated, directly reduces/decreases Zinc ion inhibition of the NMDA pathway; effectively restoring memory functions and proper expression of the NMDA receptor/s (7).

Activating the protein isn't exactly simple - as there isn't a specific drug to directly activate it. However, there are other various supplements and endogenous modulators that can be manipulated to do so. 

The first method, which is not sex-specific, would be a combination of Pregnenolone and DHEA Sulphate. These two hormones are easily available over the counter or over the Internet and they act in similar ways.

Pregnenolone acts as a positive allosteric modulator of the NMDA-receptor; and effectively displaces antagonists from binding with it - thus removing some inhibitory influences (8) (9)
DHEA/DHEA-S on the other hand, directly stimulates tyrosine kinase/Src to reduce the Zinc block on the NMDA Receptor (10) (11) (12).

Finally, increasing Testosterone, or more specifically, the male-hormone 5-alpha-dihydrotestosterone (DHT) - directly increases Src gene activity and directly amplifies/increases NMDA receptor activity; especially in the Hippocampus where it is needed most (13) (14).


My recommended {SAFE} methods of completing this Task are to use a Proven DHEA/Pregnenolone combination in a transdermal solution (Cream/Gel). Oral DHEA/Pregnenolone shows very LOW bioavailability (!).





For the DHT-part, you could also use Tribulus, but it would be *MUCH* weaker than using the Gel, I don't even know if it would be effective for this task (Probably Not)..



FINAL NOTES : Pregnenolone also blocks GABA-A Receptors in specific portions of the Brain which may be one additional mechanism by which it enhances/allows for the activation/re-activation of NMDA-Receptors and it's descending pathways.

Thursday, January 21, 2016

The Words and People we Fear are the Very Tools That Guarantee Success, Fear is a Diversion, a Subtle Attempt at Separating Us from Our Dreams

1/21/2015




I've found it was the very words I fear were the door's to success, the tool's to unlock, my Aspirations...It was that dark spirit - who has used name's and word's, and meshed them with Fear - acting to 'lock 'em Away from my Observations - so that I could not see what dreams could Appear. I see now that titling and categorizing the familiarities of my Judgement is exactly his plan to keep me away, to separate me from my Dreams.

The division from those of whom turn out to be the best ideas, the  inclination to optimism is being suppressed by the lingering doubt caused by false aversion.

Thus the title, 


The Words and People we Fear are the Very Tools That Guarantee Success, Fear is a Diversion, a Subtle Attempt at Separating Us from Our Dreams

It is my aspirations that suffer, but my Insight of People, my Insight into People's Desire, my Insight in predictability and fulfillment - these are the things that miss a Vital Piece when I am kept under the {| ILLUSION |} that my best Allies are the subject of Diverse Manipulation and / or the Receiving Ends of Spirit Trifling and Residual & Unwarranted Panic.

Methiothepin - Mechanism of Action / Pharmacology / Binding Profile (Area-1255:RC/OD Listings)




METHIOTHEPIN BINDING PROFILE {ACTIVITIES}
  • 5-HT1 Antagonist w/ Highest Affinity for 5-HT(1)B/D Receptors (1) (2).
  • 5-HT2 Antagonism (Potent @ 2A/2B/2C, but lesser than type 1B/1D) (3) (4)
  • Alpha-1-Adrenergic (Adrenaline) Antagonist  (possesses vasodilating properties) (5)
  • STRONG Dopamine D(2) Antagonist (displaying anti-psychotic properties/actions) (6) (7)
  • STRONG Anti-Histamine (H1-Selective; Producing Sedation, limiting usefulness in cognitive paradigms) (8) (9) (10) 
  • Lesser, but significant affinity for 5-HT(6/7) Receptors (11) (12) (13) (14)



Methiothepin Specific Interactions

Wednesday, January 20, 2016

How to DOWNREGULATE (Decrease) Serotonin 5-HT6 Receptors by Supplements & / or Pharmacological Methods



5-HT(6) Serotonin Receptors are GPCR's (G-Protein-Coupled-Receptors) that are positively coupled to adenylyl cyclase/adenylate cyclase which then increases the levels of cyclic adenosine monophosphate (cAMP) (1) and also they enhance the GABAergic signal which leads to inhibition of several neurotransmitters (2)...



  • They markedly decrease cholinergic transmission (acetylcholine) (3)
  • They decrease glutamate levels widespread (4)
  • They decrease dopamine in the frontal cortex and limbic areas (5).
  • They exert differential regulation patterns in the medial amygdala and thalamus however, they play little role in HUMAN endocrine functions despite their positive role in the production of cAMP (6) (7) (8).

Thus, decreasing the number of (downregulating) these ((5-HT6)) Receptors will IMPROVE Memory, Mood, Motivation and general mental integrity by all-round improving neurotransmission in almost every brain region.



5-HT6 Serotonin receptors are regulated by TWO Primary mechanisms.



The EASIEST way to address BOTH of these issues is to use ANIRACETAM, a nootropic supplement of the 'Racetam' class; this will downregulate 5-HT6 by the glutamate pathway. 

ANIRACETAM can be purchased @


The next SECRET is to DOWNREGULATE or otherwise BLOCK ESTROGEN Activity/Level's as Estrogen interacts with the corticosteroid pathway and also stimulates 5-HT6-receptor Activity (13) (14).



  • Check hormone levels in blood work to make sure Estrogen (E2) isn't already low.
  • Check out Arimidex; the only proven way to decrease estrogen significantly in both men and women.
  • ANOTHER REASON for Men to NOT LET Estrogen run rampant in their bodies!!
  • Take a Testosterone booster to improve Memory/Cognitive function.




What Neurotransmitters are Imbalanced in a Sex Offender ? (Inside the Brain Chemistry of Sex Offenders, Pedophiles and Deviants)




Pedo's and Sex Offender's ; easily the most shunned, distasteful, repulsive and hated creature's of society ....but what makes them who they are??


Part of it is certainly brain chemistry, and part of it is upbringing..and other parts..well, IDK - but the reward circuitry hasn't developed properly in these sad fellas' brains. That's for sure.



HERE WE GO

Herbs to Stimulate Hypothalamus & Pituitary as well as Increasing Nerve Activity in the Hypothalamus

While there are a great deal of dietary, Exercise inclusive Regimen's/Protocol's to INCREASE/RESTORE HPG/HPTA Function/s - most of these FALL SHORT of being effective in real-life scenario's and in moderate impairment due to an atypical barrage of attacks against our gH/HPA neurons.

The existence of Estrogen-like compounds in many plant's makes it difficult to generalize one group of herb's or plant compound's to both Men and Women.

With that being said, I've dug pretty far in the Medical Documentation and Study's to find what I believe are the greatest candidate's -OUTSIDE- of that which we commonly hear about and what is partitioned as a 'stack' in some 'best-selling-supplement'.

Instead of rigorous mountain-high hype - I've constructed a much more gender neutral but not gender-oblivious supplement regimen.

Each of these will list the proper citations referring to their respective medical applications and these references will be in parenthesis ( ) .
By clicking on the ~NAME~ of the Herb you will be taken to the respective product page.


  • Schizandra Chinensis : This herb stimulates the hypothalamus by directly increasing Dopamine and it's metabolites as well as by regulating hormone receptors. (1) (2) (3)
  • Shilajit Paste : This is an ancient composition of elements found in Old Cave's, Mountain's and in some area's where there are small spring's and mineral-dense fountain's. It decreases the levels of Serotonin and promotes the release of Dopamine thus creating a favorable balance of hypothalamic nerve activity. (4) (5) (6) (7) (8)
  • MUCUNA PRURIENS EXTRACT : This one is also known as ''Velvet Bean'' and perhaps is a little more heard of than the above two but IMhO is **slightly** less effective. It strongly boosts dopaminergic and tryptaminergic function which leads to a better functioning HPA-Axis. (9) (10) (11) (12) (13) (14).

Monday, January 18, 2016

How to Counter Yohimbine (YOH) Side-Effects with Supplements (Sups).




Yohimbine is a tough stake to nudge in term's of it's overall effect transmission ; it has a distinct mechanism of action and distinct effect model which makes it undoubtedly one of the most profound psychoactive 'fat burning' supplement compounds.

Of these effects , Tachycardia (fast heart rate) is not deemed one of the vast benefits.. nor are ...


  • Panic Attacks
  • Anxiety
  • Worsening or Causation of Seizure's.
  • Cold Hands and Feet
  • Fearfulness/Ruminations
  • Agitation
  • Blood Pressure Elevation

With that being said, depending on the dose you take , there are very EASY methods to block most of these 'side-effects' ..including the fast-heart rate.

I'll go into the supplements first this time - then read on forth about the reasons and mechanisms by which they do their work.

**THESE ARE NOT DETOXIFICATION METHODS LIKE CHARCOAL, BUT RATHER, PHARMACOLOGICAL AND DIRECT MANIPULATIONS TO WORK AGAINST THE NEGATIVE INTERACTIONS OF YOHIMBINE WITH CENTRAL NERVOUS SYSTEM RECEPTORS**


To BLOCK / REDUCE {(YOH)} induced HIGH HEART RATE
(Blocking/Reversing Yohimbine Tachycardia)

  • L-Lysine (5-7 grams at Least)
  • Drink a Bob Marley's Mellow Mood,..or two.
  • Keep either a fast-acting benzodiazepine or , preferably, a beta-blocker on hand for severe cases.



BLOCKING YOHIMBINE INDUCED ANXIETY / PANIC




COLD HANDS / FEET
(this is a side-effect from VASOCONSTRICTION)

  • For this one, we might need something a little more elaborate, such as Icariin.
  • Something indirect, that decreases or augments noradrenaline levels; such as an alpha-1-blocker - of which won't diminish  Yohimbine's benefits; but rather, enhance them.
  • Oddly enough, Tadalafil (Cialis) might also amplify the benefits while blocking the negative's of Yohimbine.

I'll leave the source right   {HERE}.




Monday, January 11, 2016

Natural / Pharmaceutical CB1 Antagonists (Natural/Herbal Cannibinoid-1-Receptor Blockers)


CB1-Receptors are a class of Cannibinoid-Receptors (which bind endocannibinoids and THC) - they are densely populated in the Hypothalamus and Hippocampus (1) (2) - since the hypothalamus is implicated in feeding behavior/human appetite - and due to the Projection of CB1-neurons to the mesolimbic dopamine pathway - CB1 antagonists have been developed to help curb appetite and treat Obesity (3) (4).


THINK : Marijuana causes ''the munchies'' or ''extreme cravings'' which then leads to dramatically increased food consumption.

Additionally, CB1-receptors impinge on GABA-ergic cell bodies and PVN/MPOA neurons which govern sexual functions; inhibiting penile erection in men and arousal in females (5) (6).

By antagonizing (blocking) CB1-receptors; one can expect enhancement of sexual function/s and increased Testosterone levels as well (7) (8).



NATURAL CB1 ANTAGONISTS INCLUDE

PHARMACEUTICAL CB1-ANTAGONISTS







Sunday, January 10, 2016

Symptoms/Signs of High And Low Endorphin Levels (Including Psychological Manifestations) (Symptoms of High/Low Brain Opioid Activity)


Area-1255 : is here again with another 'outside the box' article. This time we will be exploring the differences between high and low endorphin symptomology ; this will give us a sort of 'routine' to deliberate on before making any particular medical decisions and / or consultations.


*MANY* (but not all) endocrine disorders (hormone disorders) stem from dysfunctional opioid systems (1) in the Brain, Spinal Cord and Peripheral Nervous System (2). This includes receptor downregulation and / or supersensitivity (3)


This is demonstrated, not just in opioid dependent individuals but Also those with congenital (from birth) opioid-receptor mutations/polymorphisms (4) (5) (6) (7).

Here we will go over the acute and long-term effects of physiological opioid-function abnormalties and endorphin imbalance/s.

The SYMPTOMS of Very HIGH Î²-Endorphin and / or DYNORPHIN levels (includes naturally or genetically) are...

  • Social Isolation, and low social motivation (8) (9)
  • Impulsivity (due to excess Kappa/k-opioid activation, dynorphin mediated) (10) (11) (12)
  • Depression or Anhedonia (Emotional Numbness) (13) (14)
  • Low/Absent Sex Drive (15) (16) (17) (18)
  • Low Testosterone / Universal Hypogonadism in either Sex (19) (20) (21) (22) (23) (24)
  • Infertility : in both Men and Women ; Low Sperm Count, Lack of ovulation (25) (26) (27) :-: (28) (29) (30)
  • COGNITIVE INFLEXIBILITY (unable to switch Tasks easily and unable to understand or unwillingness to Internalize what one is not used to; unable to pick up new 'concepts' and generally resorts to what one knows) (31) (32) (33) (34) (35)
  • Indifference, lack of competitive behavior, doesn't care about 'Winning' or 'Losing' (36) (37).
  • EXTREME FATIGUE / LETHARGY (38) (39) (40) (41)
  • Lack of the Ability to ''Cry''. (42) (43) (44)
  • Constipation (45) (46)

To correct most of those issues you must.
  • Resolve the underlying hormonal imbalance (too much Progesterone or Estrogen etc)
  • Use Naltrexone in the short-term if no anxiety disorder is present. (25-50 mg once per day)
  • Use Cialis to counter-act the sexual deficits in the short-term. (5-20 mg once per day)



TO Permanently SOLVE Opioid IMPOTENCE & Sexual Deficit as well as REVERSING/CORRECTING NATURALLY HIGH OPIOID-ENDORPHIN AXIS LEVELS, simply Click the ~Image~ below.








The SYMPTOMS of Very LOW Î²-Endorphin and / or DYNORPHIN levels (includes naturally or genetically) are...



  • Anxiety; especially anticipatory Anxiety (47) (48)
  • Residual Ruminations (feelings of excess/persistent dread or tremor after traumatic/stress event/s) (49)
  • Risk-Taking Behavior (living ''on edge'') (50) (51)
  • Loves working Out; sometimes to the Point of 'over-training'. (52)
  • Workaholicism and Fast, Intuitive, Bright and Dedicated mind, but with underlying internal anxiety and persistent emotional fastening/Reservations. (53) (54) 
  • Depressive, even Suicidal tendencies in *some* individuals Affected. (depends on other factors; such as psychosocial status , income, past experiences and personality traits as well as belief system influence/s) (55)
  • Rigorous 'testing' or even compulsive behavior; constant checking; O.C.D (!)

**It is important to note that both high and low beta-endorphin levels can lead to obsessive-compulsive disorder**.

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