A Standard Method to Understand Neurochemistry’s Complexities

By Herb Wiggins, M.D.; Clinical Neurosciences; Discoverer/Creator of the Comparison Process/CP Theory/Model; 14 Mar. 2014
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In the field of neurochemistry it has been estimated that there are about 100 neurochemicals or so operating in the human brain. How to understand all of these complex system neurochemicals and how they work? The method has been understood and is therefore easily applicable in all the myriad ways.
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First of all, these descriptive methods use comparison processes and methods, the Least Energy rule, structure/function relationships, & complex system thinking. Essentially, description is the application of relatively efficient concepts/words which act as standards against which we can describe events in existence. The close correspondence between those ideas and the events to which they relate, describe, and detail processes is the critical insight here. Because once this descriptive model is largely developed into a working model, then it can be in part mathematized to greater define by measurement what’s going on, and can be more precisely tested and thus described.
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But First comes the model, which we learn from Einstein. Mostly descriptive, just as Newton’s first inklings of gravity were visual, process thinking, it was developed and lastly mathematized by Einstein and Minkowski. Note, please, this sequence. Creating the model from comparison methods and least energy real existing principles, to give it the empirical nature it must have to be real and useful, and then mathematizing it where possible.
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This is also seen in the way our linear measuring scales take our sensory systems and create high, higher, highest, and low, lower lowest. Taking the synonym/word cluster of height, length, width, altitude, size, etc., and creating a standardized, relatively fixed, efficient method, that is, convention (standard), by which we can use to describe events. Thus we created first the span, foot, etc. measuring tools. Then a more English system, Also using “hands” for measuring horse heights at the shoulder; and finally, the metric system which embodied the decimal system for efficiency, which easily replaced all the others for least energy reasons. Thus the cubit, to the foot, to the mile, to the meter, etc., development, all least energy driven.
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For temperature we use the efficient, easily duplicable freezing point and boiling points of water, and the Fahrenheit system, for describing warm, hot, hotter, hottest, and cool, cold, colder, coldest, all linear, verbal scales. The corresponding degrees Celsius/Fahrenheit, etc., does this.
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For speed & velocity, rate of expansion, etc. we use the comparison ratio of length/time. For time we use the second, minute, hour, day, week, month, year hierarchies, as well. And on and on, the myriad ways of La Chanson.
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Just so we use comparisons of an efficient description standard, thus to understand much better how the neurochemicals work. Correspondingly and consistently we use the best, oldest, most wide spread neurochemical as that standard to compare, describe and measure the other neurochemicals. (as we use the pain killing power of morphine as the efficient standard against we compare pain killing analgesics of ALL forms, for instance, using a direct ratio of pain killing power)..
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Thus we describe in detail the characteristics of the complex systems of dopamine (DA) as our standard. & using that to develop and compare against the characteristics of serotonin (5HT), GABA, and neurokinins. And describe the sedatives which act via GABA and Serotonin pathways, and the nicotinic, dimethylxanthines (caffeine, theobromine, etc.) and strychnine, as well. These act in excitatory ways, analogues of DA and the other two family members of the catecholamines, adrenaline and noradrenalin, derived from the DA, the older, parent chemical.
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In the same way, the other synthetic and artificial stimulants can also be compared to the catecholamine standards to understand their variations on this theme. This is how it’s done.
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How do we do this? Dopamine is the oldest neurochemical of import. We know this by the existence of by usual means, 10 receptor sites, D1 being motion, and E-motion being D2, generally tho there is some overlap. In addition it takes 1000’s of years of evolution to create new receptors, which are protein mediated sites on cell membranes, usually. But also we know that DA is the parent neurochemical of both norepinephrine and epinephrine (adrenalin), the latter being very powerful. But both NE and Epi have DA effects, as well. This is because we raise BP in patients by DA infusion, and also that it increases heart rate, too, which are Alpha Adrenergic actions. Beta adrenergic effects are smooth muscle relaxations to some extent, also mediated by DA. Therefore the 5-6 adrenergic receptors are ALSO DA mediated subsets. In addition, epi, being complex system, with a number of effects creates immune system effects, pain blocking, as well as increasing blood sugar. There are others, as effects on immune system being anti-histaminic and treating anaphylaxis, successfully and on a very quickly responding, emergency basis. & nausea, emptying of bowels, too. Anorexia is also a trait associated with the catecholamines, too. This gives an idea of how central to the CNS the whole system DA and its daughters, NE and Epi, are. And how the central, standard/convention of DA can create an understanding better of the catecholamine family of relationships, from the start. And thus can be extended easily by comparison to each of the other major neurochemicals and their synthetic, pharmacological analogues.
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In addition, nicotinic actions and receptors are known. But this is the cognitive dissonance: there is NO nicotine normally in brain. So what acts at those receptors? And how do we explain the nicotinic agonists of epibatidine and tebenacline which block pain at 200 and 50 times respectively the mg./mg. comparison with morphine?
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As written about before, what of the motor nicotinic, Ach receptor sites? That cannot be because unlike insects, there is not wide use of nicotinic sites, which is why the insecticides are very often Ach inhibitors as well and the nicotine is also insecticide. As might well be chocolate, theobromine and theophylline which can poison many animals, too. & human babies if not careful  & further there is NO nicotine in the brain. Thus we begin to see the overlap, the commonalities of the excitatory normally occurring receptor sites of DA and excitatory neurochemicals, as well. And using this method, we see that the nicotinic sites are very likely most closely related to DA and the catecholamines systems.
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In addition, in pain killing power, DA ranks very high. As does adrenalin, as anyone who’s been seriously wounded knows. The flight or fight outpouring response of adrenalin, DA, cortisol, anandamide, kills pain wonderfully, for about 20′, allowing us to get away. and THEN we start feeling the pain. DA and related neurochemicals kill pain, and do it convincingly. Block the DA, and the pain recurs. Use naloxone and the pain killer is blocked. Use epibatidine and tebanicline (ABT-594) and the pain is blocked as those are nicotinic agonists. But recall, there are NO nicotine chemicals in the brain known, only DA!!!
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Thus DA & related are pain blockers, largely, and we can measure those against the power of DA as well, or Adrenalin if we choose. As we currently use the morphine standard of pain control per milligram, when compared to the other pain drugs.
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DA is a stimulant. It wakes us up, and activates the awakening of the nervous system. It has the D1, largely the motion, and D2, largely the E-motion (no coincidence there, but a widely missed point in neurophysiology). When DA is given for BP drop, to support perfusion, we see that not only does the BP rise, with the heart rate (adrenergic Alpha receptor stim, but also that the person wakes up some times from the coma!!!
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n the Balanced Brain we have the interplay between serotonin/5HT, GABA, and neurokines in terms of sleep/wake cycles, the circadian rhythm, mediated by DA and 5HT. And the pain system, mediated by the stimulant, neurokinin, which will NOT rest & unfailingly reminds us until we feel and deal with the pain, effectively. It’s a stimulant, like nicotine and the catecholamines, whereas serotonin is inhibitory, with all the shades of grays. Thus neatly accounts for the kinds of circadian rhythm problems, the migraine HA’s which are DA and 5HT mediated, and the pain complex system, as well.
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GABA is an inhibitory neurochemical and its sedating effects, like those of chlorpromazine, a standard DA inhibitor, are like serotonin, but with differences. GABA agonists block Seizures as well. Serotonin enhancers do NOT create seizures. But low 5HT activity/levels seen in migraines explain the 10% incidence of seizures with migraines, as well. And the seizures created by adrenalin and nicotine are well described. These complex interactions and their confusing mass of effects, are largely all standardized and made organized by comparison with the DA effects, and functions.
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Thus we begin to see how we can understand the other neurochemicals from the complex system, multiple receptor sites of DA (and Those receptor site multiplicities, all the myriad ways), show us the complex system nature of receptor sites. (Just as the Lorentz/Fitzgerald equations were NOT how the universe looked without the putative ether, but were quite instead measures of how fermions were affected by speeds near that of Cee, as Einstein showed), so are the receptor sites clear cut, obvious insights into the complex system nature of physiology, including neurophysiologies and neurochemicals. That relationship is at once evident when the new epistemology, the comparison and LE insights are applied.
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In addition we often speak of “side effects” of drugs. In other words those effects which are not what we’re looking for, and which render some drugs useless because of those “untoward” effects. Very likely just like receptors sites show, the so called “side effects” are but linear simplifications & are NOT side effects, but more accurately complex system effects. This is how we use more advanced comparison standards to extend, improve and make more efficient our understandings. & each of those complex systems are NOT to be ignored by linear methods, but they show us the many capabilities of such drugs, which we can use to design more effective medications, doing more with less.
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As the method which can make Sildenafil 50 mg. tab last for 3 days in responders to the usual dosages and linear, “take the pill” model. Just as l-dopa with carbidopa, or amoxicillin with clavanulate (a beta lactam inhibitor), are far, far more effective with fewer “side effects” than without. This shows the way, frankly, to a new pharmacology of complex systems, which unbeknownst to most pharma, they are going towards with methods used to treat depressions. Many new depression meds have multiple effects built into their molecules. Thus, in this complex system way, much is done with less.
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we find, as in the “Balanced Brain” that our early medications did not treat all of the disease processes, such as hypertension, depressions, and migraines. But as we found out, there are many aspects to migraines, being complex systems, and careful, trial and error testing showed that taking a complex system approach using meds to block the DA, 5HT, and neurokinin pain AND anti-inflammatory effects of migraines were necessary to control migraines better, and often prevent them.
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This brings out the DA spectrum of effects in the motions & emotions. The production of dyskinesias, parkisonisms, and related movement disorders and the related emotional disorders at the high end of DA activities, mania/psychosis. Then down through the more normal range of the sociabilities of the species, love, charity, altruism, hope, faith, optimism, and the qualities of mercy in the largely D2 category. Altho those do overlap with D1. However, the creating of DA blockers to leassen the D1, and amplify the treatment of D2, by fewer “side effects” (ahem!), we find better emotional control of manias and psychoses, and now we know more clearly why. Complex system effect models again. And the addicting effects of DA and related neurochemicals, such as endorphins, used for pain control as innate DA pain blocking analogues.
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And this is how we do it, as the “Balanced Brain” shows, comparing DA and 5HT in both the very ancient circadian rhythms, and in also, 5HT complex of migraines, plus an addition benefit of understanding HOW pain comes about (neurokinins, excitatory, similar to DA) and pain control, too. Why we use Anacin for pain (ASA PLUS caffeine), as in Caf-ergot, as well. Thus much more is explained by this model than can be otherwise efficiently and simply understood.
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So we use almost all the DA effects to understand as well, morphine, endorphines, and anandamides (THC, marijuana analogues). Thus the entire model is quite a bit simpler, unifying and explains a very great deal with a little. A good model in fact.
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There is much, much more, such as understanding Seizures as hyperexcitabilities and why the post ictal period is a sleeping state. And how the alpha, beta, and theta measure what’s going on. Alpha as the brain synchronizers, and so forth. Beta as a measure of the inhibitory circuits and serotonin type acting drugs, and GABA as a sedative, and DA inhibitors, relatively. The GABApentins being used as seizure medications, also fits quite well into this larger model, too.
Then each the neurokinins and their affects, inflammation, long lasting enduring pain (get the migraine treated ASAP to avoid a long, drawn out headache), and why many sedatives which induce sleep will break up a migraine HA, too. It all fits into the larger neurochemical picture. Simply by adopting a good, general, basic neurochemical standard to start with, and then as the major characteristics of each, 5HT, GABA, neurokinin, Anandamide, Endorphins, etc., are compared to DA are found, Establishing each of those new ideas/concepts/names as better standards by which we can explain, extend & continue to build on the great numbers and complexities of the neurochemicals.
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That’s how it’s done. Creating an Einsteinian, relatively fixed, stable standard, against which we describe and measure the neurochemicals, en masse, AKA the DA standard. Thus does the comparison model create progress towards a unified understanding of all those scores of neurochemicals. A method which creates understanding by showing the relationships of neurochemicals to each other, using the DA standard as the convention/standard, measure of the others. Creating new words/standards by which our understanding of neurochemistry is advanced, as well.
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Then we use the 5HT, GABA, and other effects of each of the neurochemicals compared and described next to DA, as MORE standards against which we can such as 5HT compare to similar inhibitory and excitatory neurochemicals.
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And quite within and consistent with the comparison process and methods, least energy, structure/function relationships, and complex system models work..
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Simplifying comprehensive, without limits in terms of understanding depression as low DA, and so forth. And WHY beta blockers create depression in some and why having small pets around are anti-depressants, among other methods.
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