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

---------------------------------------------------------------------TeamTLR HomePage--------------


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].

KETANSERIN TARTRATE - An Incredibly Viable Serotonin Antagonist / Alpha-Adrenergic Antagonist Compound with ANTI-HYPERTENSIVE, Anxiolytic & AntiDepressant Effects

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  KETANSERIN. 

----------------KETANSERIN TARTRATE can be purchased of 99%  PURITY @TeamTLR below------

http://teamtlr.com/neuropsychochemicals/75-ketanserin-tartrate-.html

---------------------------------------------------------------------TeamTLR HomePage--------------

 KETANSERIN

Ketanserin is an extremely potent 5-HT2A antagonist; showing 2.01 Ki (nM) affinities for human 5-HT(2)A receptors (1) (2), the nearly unsurpassed affinity and near total selectivity for the 2A receptor over other serotonin subtypes, confine ketanserin to one of the most or most viable serotonin antagonist compounds. 

Many other drugs have some semi-appreciable affinity or even very potent affinity for the 2A receptor (but the majority don't run close to ketanserin) , but the problem is their clinical use for conditions specifically involving this receptor (or for research) are limited due to their occupation of other receptors across multiple other neural networks and neurotransmitter systems(3).

Examples include, anti-psychotics, tricylcic anti-depressants, and some anti-migraine drugs. 

However, some of the therapeutic use of medications in the above classes seems to be partly rooted in their 2A antagonist properties...which prompted further studies with ketanserin(4)(5).

Ketanserin is shown to improve brain derived neurotrophic factor release, especially if coupled with other serotonergic agents or some modulators(6)(7).

Ketanserin also decreases nicotine self-administration and thus may be useful as a quit smoking aid or augment to a quit smoking regimen(8).

Ketanserin is also highly efficient in reducing hypoglycemia and stress induced increases in Prolactin (PRL) Cortisol and ACTH, making it a powerful anti-stress and hormone preserving compound(9)(10). 

Back to the main topic at hand..ketanserin has powerful anti-depressant effects, and it can be an excellent augment to traditional anti-depressants and to lesser known, tricylclic or NaSSa anti-depressants. A large paper was written by the Indian Journal of Pharmacology , in late 2014 (just last year) , demonstrating the effects of ketanserin on escitalopram treatment. When adding ketanserin, behavioral abnormalties induced by the SSRI, along with other side-effects such as hyper-emotionality and decreased spatial performance were ameliorated/reversed(11).

Additionally, signs of mania in other , more central 2A studies were demonstrated to be reduced, and this is also consistent with the use of other psychotropic agents with affinity for the 2A receptor, being utilized in bipolar depression and mania alone(12) (13).  

Ketanserin is such a strong 5-HT antagonist, that it was able to relieve PSILOCYBIN-induced deficits in behavioral inhibition (14) as well as blocking overstimulation by LSD , which speaks for it's potency as the comparison substances are pretty damn strong!!

Obviously, if one's goal is to study and / or experience the effects of hallucinogens, then ketanserin is a one way street to blunting the effects, but that doesn't nearly equate to uselessness.

Ketanserin also shows anti-Psychotic properties itself (15) (16), because of the above, and even greater, ketanserin can COMPLETELY REVERSE anti-psychotic drug induced catalepsy (17) !!

Finally, ketanserin shows immense promise for immediate and persistent treatment of high blood pressure. It's pharmacological properties allow for treatment of HBP incidences due to both adrenaline excess as well as serotonin excess. To date, there aren't any real standalone drugs that act on serotonin receptors to reduce blood pressure, at least not solely. This one is valuable and diverse, and thus represents a novel strategy for targeting multi-pathology hypertensive occurrences(18)(19). 


In conclusion, results with ketanserin are VERY promising, making it an ideal candidate for.

• Alleviation of high blood pressure from both serotonergic and adrenergic excess. Alleviating stress induced hypertension.
• Reduction of stress and hypoglycemia induced cortisol, ACTH and prolactin release. Optimization of hormone parameters.
• As a behavioral modulator, reducing mania and psychosis.
• As an anti-depressant and anti-depressant therapy modulator/augment.
• Reversing behavioral inhibition (anxiety) and overstimulation due to hallucinogenic drugs.
• Reducing nicotine self-administration and thus a suitable tool as a quit smoking aid or in the development of regimens for this purpose.
• Helping to alleviate anxiety disorders .

Optimoterol - The debut of superior β2 receptor agonist/cardioselective β1 receptor antagonist Proprietary Blend-OA

Move over Clenbuterol and Welcome OptimoterolTM

The debut of superior β2 receptor agonist/cardioselective β1 receptor antagonist

proprietary ratio combination as an Optimized Agent format.

Potent and highly efficacious combination of Formoterol and Nebivolol in an optimized ratio format for research into the benefits of the potent β2 agonist Formoterol while using an optimum correlative dose of Nebivolol to promote minimized adverse effect potentials via cardioselective antagonism of β1 receptors.

Optimoterol

Optimized Agent design to provide the most superior efficacy and therapeutic index for the spectrum of benefits.

Research Indications:  Anti-Obesity/Lipolytic Research, Anabolic/Myotrophic Research, Neurogenic/Dendritogenic Research, Anti-Aging Research, Mitochondrial Research

Formoterol is a long-acting β2 agonist (LABA) that has an extended duration of action (up to 12 hours) compared to short-acting β2 agonists such as salbutamol, which are effective for 4–6 hours.

Nebivolol is a cardioselective β1 receptor antagonist with a mean half-life of about 12 hours.

Enhanced Muscular Hypertrophy and Anti-Obesity Potentials: Potent Lipolytic Effects with Concurrent Anabolic-Myotrophic Effects

β2 agonists increase energy utilization and fat metabolism, however, therepeutic use for obesity has been limited by the concomitant activation of β1 receptors resulting in excessive increases in heart rate. A recent 2012 dose-finding study (in healthy men) demonstrated significantly increased resting energy expenditure, and fat oxidation at a dose of 160 μg of formoterol per day without significantly increased heart rate. Formoterol's specificity for the β2 receptor (relative to β1 receptors) may facilitate its use for this purpose. A combination of a highly selective β2 agonist like formeterol with a low dose highly selective β1 blocker may further improve the differential therapeutic ability to selectively agonize β2 receptors for metabolic benefits in treating obesity without adverse β1 agonist effects.[1] The selective β1 blocker (β1 antagonist) Nebivolol at low doses results in fully cardioselective effects and demonstrates efficacy to abolish potential adverse effects of formoterol at higher doses. Nebivolol demonstrates antihypertensive vasodilatory effects as well.

As with other beta(2)-adrenoceptor agonist (beta(2)-agonist), formoterol, has been shown to cause muscle hypertrophy in rats even when administered at the micromolar dose of 25 micro g/kg/day. A similar low dose of formoterol as well improves muscle function in the dystrophic mdx mouse. The findings indicate formoterol has considerably more powerful anabolic effects on skeletal muscle than older generation beta(2)-agonists (like clenbuterol and albuterol), and has considerable therapeutic potential for muscular dystrophies and other neuromuscular disorders where muscle wasting is indicated. [2]

::  MECHANISM OF ACTION :: 

Beta-adrenergic agonists may help build muscle through two mechanisms.

1.) They may increase androgen signaling through induction of histone demethylase (!) (!) which leads to increases in androgen receptor signaling (!). When androgen receptor signaling is increased, protein synthesis, utilization and delivery is dramatically enhanced. Additionally, the anabolic benefits of androgen receptor activation may be furthered when glycogen uptake is improved, which also occurs with beta agonists.(!) 

2.) They inhibit myostatin, ESPECIALLY formoterol(!), have you seen the rats, swine, and cows who have myostatin genes deleted? They are hunormous! (!)

By inhibiting this enzyme, muscle growth is DISINHIBITED and other anabolic hormones are also then disinhibited. Thus, everything else you do will result in higher results and strength will be improved dramatically as muscle growth is accelerated. You see, because myostatin is an enzyme/protein complex that is almost solely around to control** muscle growth(!).

ANABOLIC EFFECTS ON BONE
Formoterol - may also have anabolic effects on bone and thus lead to expansion / growth of cortical bone , it may also , with long-term use - lead to increases bone mass and density(BMD/BDD).  (!) (!) (!)
The PKA/cAMP pathway leads to increases in osteocytes and osteoclasts and also increases enzymatic growth factors including IGF-1, Transforming Growth Factor and Bone Morphogenic Proteins. The complex alteration in signal transduction leads to widespread beneficial enhancement in growth factors both in bone and in some cartilage.

Anticachexic Potentials -  results indicate that formoterol exerted a selective, powerful protective action on heart and skeletal muscle by antagonizing the enhanced protein degradation that characterizes cancer cachexia, and it could be revealed as a potential therapeutic tool in pathologic states wherein muscle protein hypercatabolism is a critical feature such as cancer cachexia or other wasting diseases.

Neurogenic/Dendritogenic Potentials: Strengthening of Nerve Connections in Hippocampus

Preliminary research offers hope that formoterol may be a useful treatment in Down's Syndrome. In a mouse model of the disease, the drug strengthened nerve connections in the hippocampus, a brain center used for spatial navigation, paying attention and forming new memories. [4]
Beta agonists also have the ability to increase glutamate levels (!)  (!) and activity in cerebrocortical nerve terminals which may improve memory and mental performance. They also appear to do so safely.
In the central nervous system, adenylyl cyclases regulate many cellular processes in response to extracellular and intracellular signals such as hormones, neurotransmitters, and Ca2+ (1). Inmunohistochemical studies of adenylyl cyclase in the brain have shown a selective concentration at synapses both in presynaptic axon terminals and in postsynaptic densities (2). Consistent with this localization, the activation of adenylyl cyclase with forskolin has been shown to enhance synaptic transmission in hippocampal slices from CA1 (3, 4), CA3 (5, 6), and the dentate gyrus (7) as well as in neostriatal neurons (8). Moreover, the cAMP-dependent effects on synaptic transmission have been implicated in long-term potentiation in the hippocampus both in CA1 neurons (9) and in slices from the CA3 region (6, 10). Recently, evidence has been found indicating that the extracellular signal involved in the activation of this cAMP-dependent pathway is noradrenaline, acting via a β-adrenergic receptor. Thus, the β-adrenergic agonist isoproterenol has been shown to mimic the potentiating effects of cAMP elevation in synaptic transmission (11, 12).

Stimulation of mitochondrial biogenesis

Formoterol may also help stimulate mitochondrial biogenesis. Mitochondrial dysfunction is related to many degenerative diseases — particularly neurodegenerative disorders. Formoterol thus may provide potent an anti-aging longevity-healthspan promoting mitochondrial biogenesis.[5]
Additionally, formoterol being a beta-agonist, may improve thyroid hormone ratios and thus act on a neuro-endocrine level to boost cellular metabolism as well. Specifically the increase in cyclic adenosine monophosphate results in the rise of T4 hormones...which then leads to higher metabolic output and strengthening of both neuronal growth factors and cellular metabolism. (!) (!)

References:

[1] Lee, P; Day, RO; Greenfield, JR; Ho, KKY (May 29, 2012). "Formoterol, a highly β2-selective agonist, increases energy expenditure and fat utilisation in men". International Journal of Obesity 37 (4): 593–597. doi:10.1038/ijo.2012.90. ISSN 1476-5497. PMID 22641064

[2] Harcourt LJ1, Schertzer JD, Ryall JG, Lynch GS Low dose formoterol administration improves muscle function in dystrophic mdx mice without increasing fatigue. Neuromuscul Disord. 2007 Jan;17(1):47-55. Epub 2006 Nov 28.

[3] Busquets S1, Figueras MT, Fuster G, Almendro V, Moore-Carrasco R, Ametller E, Argilés JM, López-Soriano FJ. Anticachectic effects of formoterol: a drug for potential treatment of muscle wasting. Cancer Res. 2004 Sep 15;64(18):6725-31.

[4] Dang, Van; Medina, Brian; Das, Devsmita; Moghadam, Sarah; Martin, Kara J; Lin, Bill; Naik, Priyanka; Patel, Devan; Nosheny, Rachel; Wesson Ashford, John; Salehi, Ahmad (27 June 2013). "Formoterol, a Long-Acting β2 Adrenergic Agonist, Improves Cognitive Function and Promotes Dendritic Complexity in a Mouse Model of Down Syndrome".Biological Psychiatry. doi:10.1016/j.biopsych.2013.05.024

[5] Wills, Lauren P; Trager, Richard E; Beeson, Gyda C; Lindsey, Christopher C; Peterson, Yuri K; Beeson, Craig C; Schnellmann, Rick G (April 6, 2012). "The β2-adrenoceptor agonist formoterol stimulates mitochondrial biogenesis". The Journal of Pharmacology and Experimental Therapeutics 342 (1): 106–118. doi:10.1124/jpet.112.191528.ISSN 1521-0103. PMC 3383035. PMID 22490378

Symptoms / Signs of Too Much Serotonin / Excess Serotonin {SPECIFICS, EASY TO READ, CITED}

Due to being increasingly displeased with the difficulty in finding such information; to the average user, I have compiled a well cited guide on determining if you may have TOO MUCH SEROTONIN.

One VERY important thing to remember, is that excessive serotonin production is NOT the only way to have high serotonin, and often...excessive serotonin is due decreased breakdown of serotonin and it's metabolites. This can occur when using SSRI's along with other medications or supplements that impact the breakdown of serotonin, such as MAO-A inhibitors (ST.John's Wort), Syrian Rue, Nutmeg etc

With nutmeg, it is unlikely you will get enough of a toxic effect from using a little of the whole spice, HOWEVER, if you are using teaspoon after teaspoon of nutmeg excessively, then EATING other foods that increase serotonin, like bananas and turkey - then you have an increased risk of developing serotonin syndrome.

KEEP IN MIND, that the symptoms related to serotonin syndrome represent a SEVERE excess of serotonin which often requires immediate care / CRISIS management.

TOO MUCH serotonin is describing a PERSISTENT, but NOT SEROTONIN-SYNDROME qualified excess. Therefore, this article is NOT describing serotonin syndrome, but too much serotonin* over time - where it relates to borderline health issues.

This article is ideal for those who suspect out of balance serotonin, but not so much serotonin that it becomes toxic as in an acute CRISIS. 

Some symptoms of high serotonin mirror those of low glutamate- NMDA function.

                                  SENSORY EFFECTS

• Over-Sensitivity to sounds, especially loud noises. Excessive jumpiness or even anxiety in response to sudden sounds or movements(1) (2).
• Visual distortions, height / depth alteration, hallucinations(3) (4).
• Words may appear out of place, or your perception of what you are reading may be entirely different. { e.g reading the third line thinking its the second} (5)
• Sensitivity changes to light, sedation or no response to darkness(6) (7) (8) (9). 
• Lack of pain sensation, or HYPO Algesia, some individuals with high serotonin display such a lack in pain perception/sensitivity that it mirrors the effects of those under the influence of PCP. Pain asymbolia can be misdiagnosed as high serotonin(10) (11).
• Tinnitus, ringing in ears(12)(13).
• Vertigo. Dizziness. Room spinning(14) (15).

                   BEHAVIORAL / MENTAL EFFECTS

• Delirium. Usually including abnormal forms of panic or worry along with various disperceptions(16) (17). 
• Depersonalization. Feeling out of place, out of body, or that events or surroundings are surreal(18)(19).
• Frequent or occasional episodes of psychosis, paranoia, pathology changes, and obsessional behavior(20)(21).
• Religious delusions and religious over-engagement. (some cult leaders are hypothesized to have elevated, but not toxic levels of serotonin)(22). The best book on this is "Biology of Religious Behavior : The Evolutionary Origins of Faith and Religion".
• Unexplained agitation or inner restlessness(23). 
• Dystonia, tic-like behaviors, punding; repetitive behaviors(24) (25) (26) (27).
• Frequent crying episodes in children, unwarranted panic or extreme anxiety(28).
• Low/Absent Libido(29)
• Emotional Anhedonia / Apathy / Blunt AFFECT (30) (31) (32) (33) (34)
• Jittery, nervous hands, tremors, impatient(35) (36) (37).
• Depression , despair, lack of motivation(38) (39). 
• Reading/Comprehension deficits(40).

                      PERIPHERAL / INTERNAL EFFECTS

• Persistent nausea, unexplained/stress induced; not due to motion sickness which is more acetylcholine based. (41) (42)
• Diarrhea/IBS Symptomology(43) (44) (45). 
• Cold hands / feet(46) (47) (48) (49).
• Lack of perspiration (sweating) or too much sweating(50) (51).
• Hyperhidrosis (52) .
• HYPERTHERMIA or HYPOTHERMIA , with a higher frequency of the latter(53) (54) (55). 
• Increased suspectibility to certain viral infections; polyoma virus susceptibility and influenza response alteration(56) (57) (58).
• HYPERTENSION, HIGH BLOOD PRESSURE (59)

                                                IN BLOOD WORK

-Low testosterone/On the low end of normal.

-High cortisol.

-High prolactin.

-High ACTH

-Hypo or hyperthyrodism (high T4/low TSH or the inverse)

********************************************

CLICK HERE FOR A NATURAL SEROTONIN BLOCKER TO BOOST LIBIDO and COGNITION

What does the INVERTED ACE symbolize, what is the meaning of an upside down (INVERTED) Ace of Spades

As an ordinary ace of spades symbolises/represents death (AKA the death card), an inverted one symbolizes resurrection, or life from death. It could also mean reincarnation. Traditionally, the ace of spades is the most powerful/significant card in the deck, and the one most associated with the "collective" win. Taken under great oath as the servant of the "master player". The Ace of Spades is a masculine symbol, the inverted ace would be seen by some as neither masculine nor feminine. 

Because, as pictured below, the ace is upside down, with the stem up, it could also indicate "heading to the ground" or "heading to hell" . Alternatively, given the ace of spades has a sharp tip, it can be seen as ready to spear the ground or attack that which it symbolizes. 

If the stem or "base" is up, it could also indicate one is exposed..or it could indicate one is firmly planted in the ground, and thus is standing firm and not budging. Is an obstacle that can't be moved, is not able to be influenced and thus "HEAVILY" stubborn and weighed down by that stubbornness which can not be moved.

Finally, as an ace of spades mimics the sexual attributes or is seen cojoined in description, it can be interpreted that the inverted ace is an asexual figure, or ..conversely, it could be seen as the "inversion" of sexual attributes, or a recreation of what is seen as sexuality. Considering the body of the symbol is in the ground, it could be seen as confined sexuality as well - or strictly engaged. It could also be seen as "locked in" or covered.

Thus the following definitions of the inverted ace of spades should be identified.

• Resurrection, reincarnation.
• Genderless, asexual. Non-human.
• Heading to the ground, "headed to Hell"
• Attacking hell. Stabbing that which is below.
• Inverting sexuality.
• Heavily implanted, heavily firm in effort. Immovable. 
• Locked in. 

Gangster / Chains' Meme's - Thug Boy Meme's / UNBLEMISHED MEME'S / MEME'S WITHOUT SITE LOGO

I don't have to pretend with all my CHAINS                       Everyone's a GANGSTER UNTIL 
                                                                    

          It's TIME TO DO GANGSTER SHIT!


I am the GANGSTER, NOT YOU!!

                                        !   MUGS YOU !

10 Rules for Assessing the Value of NeuroPharmacological Studies; How a Substance will Affect You & Why

HOW TO DETERMINE HOW A DRUG, CHEMICAL, OR NATURAL COMPOUND WILL AFFECT A LIVING HUMAN SUBJECT BASED ON A PUBMED STUDY OR REFERENCE & WHY


1.) Identify what is MISSING in the study before you register what is there.

• In other words , analyze unaccounted for parameter's or factors such as age, body weight, receptor integration etc.
• Look for determining cues of result fluctuation, or possible other reasons that could substitute or mimic the effect of the substance of question. Is it a significant difference than placebo and how many regions do the compounds effect?

2.) Determine whether the effects of a substance are primarily due to indirect 'shifting of receptor activity, or whether a direct effect of signal transduction modulation at the direct level. 

• Say you are talking about a 5-HT6 serotonin antagonist, and the study of it's pro cognitive effects. The receptor is positively coupled to adenylate cyclase. Therefore, does blocking it improve cognition because of the reduction of that enzyme or because the remainder of endogenous serotonin shifts to other receptors such as 5-HT5A, 5-HT4?

3.) REMAINDER RATIO. 

• Based on the above. Is the remainder of a neurotransmitter going to have a better chance to bind to cognitive improving receptors after the 5-HT6 is blocked? To figure this out, calculate the effects of each serotonin receptor, and the ratio of pro-cognitive to generally anti-cognitive receptors...e.g 5-HT4, 5-HT5A and 5-HT1A agonists are shown to improve cognitive function, whereas 5-HT3,2A,7A,1B,1D are anti-cognitive. 

4.) Distribution of Receptors; mapped to brain regions. 

• Specific brain regions have more of certain receptors than others in the human brain, thus we have to figure out whether the more substantial effects are due to the higher occurrence of binding by a particular compound, due to more receptors to bind to. E.G , is a 5-HT6 antagonist more effective than a 5-HT4 agonist because there are more 5-HT6 receptors in the hippocampi of the human brain.

5.) Receptor CO-LOCALIZATION :

• Are the effects of agonizing a certain receptor or antagonizing it due that receptor being cross-wired or colocalized with another, e.g 5-HT6 receptors are also present on GABAergic terminals therefore is antagonizing it an actual result of dual GABA inhibition due to cross over effect. Nerve terminals are incredibly complex, and heterodimization is another key factor in receptor functionality and interactions.

6.) Have an active knowledge of basic biochemistry principles. 

• Does the substance in mention have a phenyl group, hydrazide addition, acetyl group or addition - and thus based on it's chemical principles, is it permeable to the blood brain barrier? Additionally, is it's molecular mass small enough for it to be considered bioavailable or usable by the body? Does the substance meet Lipinsky's Rule of Five?

7.) ADMINISTRATION METHOD. 

• Is the substance orally active in the study? Do the chemical properties of the substance allow it to be orally available? 
• Additionally, is transdermal or injection a better method , or 'preferred' in the study?

8.) HALF-LIFE  / ACTIVE-LIFE

• Is the substance going to have translatable effects and a feasible half-life that doesn't infiltrate convenience? Thus display modern degrees of benefits.

9.) Whether the substance is metabolized by P-GLYCOPROTEIN, CYP34, and generally how the liver can process it.

• If the substance has benefits, but is broken down too quickly or requires additional enzyme modification for it to reach consistent blood levels, then it may not be a valuable substance standalone.

10.) Whether the substances true effects are based off of co-administration in the study or it's interactions with other undocumented factors (such as hormone replacement or modification).