GABA a dance craze or neurotransmitter
Life Sci. 1983 Feb 21;32(8):879-87.
Regulation by divalent cations of 3H-baclofen binding to GABAB sites in rat cerebellar membranes.
When investigating the effects of divalent cations (Mg2+, Ca2+, Sr2+, Ba2+, Mn2+ and Ni2+) on 3H-baclofen binding to rat cerebellar synaptic membranes, we found that the specific binding of 3H-baclofen was not only dependent on divalent cations, but was increased dose-dependently in the presence of these cations. The effects were in the following order of potency: Mn2+ congruent to Ni2+ greater than Mg2+ greater than Ca2+ greater than Sr2+ greater than Ba2+. Scatchard analysis of the binding data revealed a single component of the binding sites in the presence of 2.5 mM MgCl2, 2.5 mM CaCl2 or 0.3 mM MnCl2 whereas two components appeared in the presence of 2.5 mM MnCl2 or 1 mM NiCl2. In the former, divalent cations altered the apparent affinity (Kd) without affecting density of the binding sites (Bmax). In the latter, the high-affinity sites showed a higher affinity and lower density of the binding sites than did the single component of the former. As the maximal effects of four cations (Mg2+, Ca2+, Mn2+ and Ni2+) were not additive, there are probably common sites of action of these divalent cations. Among the ligands for GABAB sites, the affinity for (-), (+) and (+/-) baclofen, GABA and beta-phenyl GABA increased 2-6 fold in the presence of 2.5 mM MnCl2, in comparison with that in HEPES-buffered Krebs solution (containing 2.5 mM CaCl2 and 1.2 mM MgSO4), whereas that for muscimol was decreased to one-fifth. Thus, the affinity of GABAB sites for its ligands is probably regulated by divalent cations, through common sites of action.
Brain Res. 1985 Jun 24;337(1):179-83.
Specific [3H]gamma-aminobutyric acid binding to vestibular membranes of the chick inner ear.
To support a postulated neurotransmitter character of gamma-aminobutyric acid (GABA) in the vertebrate vestibule, [3H]GABA binding was measured in a crude membrane preparation of chick inner ear ampullary cristae. In the absence of divalent cations bound [3H]GABA was displaced by unlabeled GABA, muscimol or bicuculline, but it was not displaced by (+/-)-baclofen. A single population of [3H]GABA binding sites with an equilibrium constant of 19.4 nM and a maximum binding capacity of 0.58 pmol/mg protein was found. These results suggest the possible existence of a synaptic GABAA receptor in the chick inner ear membranes and sustain the neurotransmitter role of GABA in the chick vestibule
Three ligands for binding divalent cations the coordination with metals ions would appear to block photo-Fenton reaction as a six dentate ligand could form with iron (iii) and no aromatic ring is present for UVA capture and electron transfer to reduce iron. This would, therefore, be expected to reduce the rate of photo-fenton reaction and act as a suppressor.
glutamate has 5 coordination sites so it can bind to divalent cations and perform photo-Fenton.
Aspartic acid also has five electron donation sites for iron to act as a neurotransmitter.
As a neurotransmitter glycine is an inhibitory neurotransmitter in the central nervous system, especially in the spinal cord, brainstem, and retina. When glycine receptors are activated, chloride enters the neuron via ionotropic receptors, causing an Inhibitory postsynaptic potential (IPSP). Strychnine is a strong antagonist at ionotropic glycine receptors, whereas bicuculline is a weak one. Glycine is a required co-agonist along with glutamate for NMDA receptors. In contrast to the inhibitory role of glycine in the spinal cord, this behavior is facilitated at the (NMDA) glutaminergic receptors which are excitatory. The LD50 of glycine is 7930 mg/kg in rats (oral), and it usually causes death by hyperexcitability. A 2014 review on sleep aids noted that glycine can improve sleep quality, citing a study in which 3 grams of glycine before bedtime improved sleep quality in humans. Glycine has also been positively tested as an add-on treatment for schizophrenia. Technical grade glycine, which may or may not meet USP grade standards, is sold for use in industrial applications; e.g., as an agent in metal complexing and finishing. Technical grade glycine is typically sold at a discount to USP grade glycine. Many miscellaneous products use glycine or its derivatives, such as the production of rubber sponge products, fertilizers, metal complexants
D serine – 4 coordination sites with iron. Two sites are available for hydrogen peroxide binding. D-Serine, synthesized in neurons by serine racemase from L-serine (its enantiomer), serves as a neuromodulator by coactivating NMDA receptors,
Glycine again 3 coordination sites with iron so 2 x glycine would cause reduced photo-Fenton chemistry. Glycine is an inhibitory neurotransmitter in the central nervous system, especially in the spinal cord, brainstem, and retina.
Dopamine capturing UV light in the aromatic ring and 3 coordination sites. Does the aromatic ring pie electrons also act as an iron coordination site? So photon capture by the aromatic ring and electron transfer to Fe(iii) via coordination chemistry via the hydroxyl, amine and aromatic ring are able to provide four of the six iron coordination centers.
Norepinephrine again the aromatic ring acts as one of 5 coordination sites with iron. It can again do UV capture due to the aromatic ring.
Epinephrine only difference is a methyl group on the amine again 5 coordination centers available for iron. The hydrogens on the methyl are potentially quantum in nature they will have a tetrahedral arrangement that could be able to capture vibrational energy at C-H vibrational frequency.
Histamine 3 binding sites or four sites dependent on the pi electrons in the imidazole ring structure. Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological function in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Histamine is involved in the inflammatory response and has a central role as a mediator of itching. Histamine is a neurotransmitter that is released from histaminergic neurons which project out of the mammalian hypothalamus. The cell bodies of these neurons are located in a portion of the posterior hypothalamus known as the tuberomammillary nucleus (TMN).
What on and off rates kinetic rates of binding metals to the various neurotranmitters? How is visual colour observed in an atom? The band gaps between energy orbitals of electrons provides energy release and a photon of light of a particular wavelength that we see as colour in an object.
3 binding sites for iron coordination chemistry
Psilocin primarily activates 5-HT2A receptors, but has affinity for 5-HT1A receptors as well. ... Additionally, psilocin may also have peripheral effects that involve serotonergic receptors.
Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. It has a popular image as a contributor to feelings of well-being and happiness, though its actual biological function is complex and multifaceted, modulating cognition, reward, learning, memory, and numerous physiological processes.
Melatonin is a hormone that regulates sleep–wake cycles. It is primarily released by the pineal gland. As a supplement, it is often used for the short-term treatment of trouble sleeping such as from jet lag or shift work.Evidence of benefit, however, is unclear. One review found onset of sleep occurred 6 minutes faster with use but found no change in total time asleep. It may work as well as the medication ramelteon. It is typically taken by mouth.
Electrosynthesis of phenethylamine from benzyl cyanide
This chemistry clearly indicates the requirement for iron in a coordination chemistry used to produce the phenethylamine. Again photo-fenton chemistry mediated interactions with the aromatic ring and the transfer of the electrons from the C-N triple bond are performed.
Phenethylamine has two binding sites for metal ion coordination. Pi stacking and the amine. Again the ethyl functionality observed which may be needed to the folding back of the primary amine to interact with the metal coordination site above the pi ring of the benzene structure.
N-Methylphenethylamine has two positions of coordination with iron for photo-Fenton chemistry.
Tyramine (4-hydroxyphenethylamine; para-tyramine, mydrial or uteramin) is a naturally occurring monoamine compound and trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent. Notably, however, it is unable to cross the blood-brain barrier, resulting in only nonpsychoactive peripheral sympathomimetic effects. A hypertensive crisis can result from ingestion of tyramine-rich foods in conjunction with monoamine oxidase inhibitors (MAOIs).
3-Iodothyronamine could be up to 5 possible electron donating groups present in this compound.
Octopamine (β,4-dihydroxyphenethylamine) is an endogenous biogenic amine that is closely related to norepinephrine, and has effects on the adrenergic and dopaminergic systems. It is also found naturally in numerous plants, including bitter orange. Biosynthesis of the D-(–)-enantiomer of octopamine is by β-hydroxylation of tyramine via the enzyme dopamine β-hydroxylase. Under the trade names Epirenor, Norden, and Norfen, octopamine is also used clinically as a sympathomimetic agent.
Previously observed that the primary amine photon (bond) which produces blue light is captured by the FAD to produce lower energy green light which is then able to fluoresce and release the photon.
The protonation of the amines is essential in the redox cycling of iron. Peptides: somatostatin, substance P, cocaine and amphetamine-regulated transcript, opioid peptides. Gasotransmitters: nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S), Others: acetylcholine (ACh), adenosine, anandamide, etc. In addition, over 50 neuroactive peptides have been found, and new ones are discovered regularly. Many of these are co-released along with a small-molecule transmitter. Nevertheless, in some cases, a peptide is the primary transmitter at a synapse. β-endorphin is a relatively well-known example of a peptide neurotransmitter because it engages in highly specific interactions with opioid receptors in the central nervous system.
Single ions (such as synaptically released zinc) are also considered neurotransmitters by some, as well as some gaseous molecules such as nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S). The gases are produced in the neural cytoplasm and are immediately diffused through the cell membrane into the extracellular fluid and into nearby cells to stimulate the production of second messengers. Soluble gas neurotransmitters are difficult to study, as they act rapidly and are immediately broken down, existing for only a few seconds.
The most prevalent transmitter is glutamate, which is excitatory at well over 90% of the synapses in the human brain. The next most prevalent is Gamma-Aminobutyric Acid, or GABA, which is inhibitory at more than 90% of the synapses that do not use glutamate. Although other transmitters are used in fewer synapses, they may be very important functionally: the great majority of psychoactive drugs exert their effects by altering the actions of some neurotransmitter systems, often acting through transmitters other than glutamate or GABA. Addictive drugs such as cocaine and amphetamines exert their effects primarily on the dopamine system. The addictive opiate drugs exert their effects primarily as functional analogs of opioid peptides, which, in turn, regulate dopamine levels.
Type I (excitatory) synapses are typically located on the shafts or the spines of dendrites, whereas type II (inhibitory) synapses are typically located on a cell body. In addition, Type I synapses have round synaptic vesicles, whereas the vesicles of type II synapses are flattened. The material on the presynaptic and post-synaptic membranes is denser in a Type I synapse than it is in type II, and the type I synaptic cleft is wider. Finally, the active zone on a Type I synapse is larger than that on a Type II synapse.
The colloid nature of vesicles in excitatory synapses provides for a lens effect which is characteristic of a spherical shape and the ability to take a photon of light and focus this at the focal point which then creates a higher eV value relating to the activation of ROS within the excitatory neuron.
The flow of ions causes a current to be generated. Electricity produces magnetism at 90-degree angle and at 45 degrees to this a photon of light will be generated. The Myelin sheath around the neuron traps the photon of light which is sent down the entire length of the neuron. This light wave propagation enables the light of various wavelengths to be absorbed by the various structures within the neuron.
Pentylenetetrazol, also known as pentylenetetrazole, metrazol, pentetrazol (INN), pentamethylenetetrazol, Cardiazol or PTZ, was a drug used as a circulatory and respiratory stimulant. High doses cause convulsions, as discovered by the Hungarian-American neurologist and psychiatrist Ladislas J. Meduna in 1934. It has been used in convulsive therapy but was never considered to be effective, and side-effects such as seizures were difficult to avoid. Its approval by the FDA was revoked in 1982.
Acetylcholine has three coordination sites for iron coordination for photo-Fenton chemistry in neurotransmission which suggests that 2 x acetylcholine would occupy all six Fe coordination sites without the ability to perform photon capture (electron capture) and enable reduction of iron from Fe(iii) to Fe(ii). This would suggest that acetylcholine would suppress photo-Fenton activity. Again this has an inhibitory effect so correlates well with photo-Fenton down-regulation.
Acetylcholine is one of many neurotransmitters in the autonomic nervous system (ANS). It acts on both the peripheral nervous system (PNS) and central nervous system (CNS) and is the only neurotransmitter used in the motor division of the somatic nervous system. Acetylcholine is also the principal neurotransmitter in all autonomic ganglia.
In cardiac tissue acetylcholine neurotransmission has an inhibitory effect, which lowers heart rate. However, acetylcholine also behaves as an excitatory neurotransmitter at neuromuscular junctions in skeletal muscle.
Valproic acid (VPA, valproate), an acidic chemical compound, has found clinical use as an anti-convulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder and prevention of migraine headaches. VPA is a liquid at room temperature, but it can be reacted with a base such as sodium hydroxide to form the salt sodium valproate, which is a solid.
The acid, salt, or a mixture of the two (valproate semisodium) are marketed under a number of different brand names, including: Depakote, Epilim, Valparin, Valpro, Vilapro and Stavzor. It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.
Two sites for iron chelation so 3 x valproate could act to stop the photo-Fenton reaction. The most common adverse effects of valproic acid are digestive complaints like diarrhea, nausea, vomiting and indigestion; vision problems like seeing double or lazy eye; hormonal disturbances (increased testosterone production in females and menstrual irregularities), hair loss, memory problems, weight gain, infections, low platelet count (which can make one bleed more easily), dizziness, drowsiness, tremor and headache. Less common, yet serious side effects include liver damage, brittle bones (becomes far more common with long-term use), polycystic ovaries, movement disorders (which may be irreversible like tardive dyskinesia), psychiatric/neurologic disturbances like hallucinations, anxiety and confusion; pancreatic inflammation, low body temperature and potentially life-threatening blood abnormalities.
In eukaryotic cells, it is required for the transport of fatty acids from the intermembranous space in the mitochondria, into the mitochondrial matrix during the breakdown of lipids (fats) for the generation of metabolic energy. It is widely available as a nutritional supplement. Carnitine was originally found as a growth factor for mealworms and labeled vitamin BT, although carnitine is not a proper vitamin. Carnitine exists in two stereoisomers: its biologically active form is L-carnitine, whereas its enantiomer, D-carnitine, is biologically inactive.
Risperidone (trade name Risperdal and generics) is an antipsychotic drug mainly used to treat schizophrenia (including adolescent schizophrenia), schizoaffective disorder, the mixed and manic states of bipolar disorder, and irritability in people with autism. Risperidone is a second-generation atypical antipsychotic. It is a dopamine antagonist possessing anti-serotonergic, anti-adrenergic and anti-histaminergic properties. The adverse effects of risperidone include significant weight gain and metabolic problems such as diabetes mellitus type 2, as well as tardive dyskinesia and neuroleptic malignant syndrome. Risperidone and other antipsychotics also increase the risk of death in people with dementia.
The drug was developed by Janssen-Cilag, a subsidiary of Johnson & Johnson, from 1988 to 1992 as an improvement from the typical antipsychotic and first approved by the FDA in 1994. Today many generic versions are available. It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.
On 11 April 2012, Johnson & Johnson and its subsidiary Janssen Pharmaceuticals Inc. were fined $1.2 billion by Judge Timothy Davis Fox of the Sixth Division of the Sixth Judicial Circuit of the U.S. state of Arkansas. The jury found the companies had downplayed multiple risks associated with risperidone (Risperdal). The verdict was later reversed by the Arkansas State Supreme court.
According to the Wall Street Journal on June 20, 2012, Johnson & Johnson and the U.S. Justice Department [we]re close to settling a protracted investigation into the company’s promotion of the antipsychotic Risperdal, for what would be one of the highest sums to date in a drug-marketing case. The sides are trying to wrap together a number of lawsuits, state investigations and other probes of alleged illegal marketing, and are discussing a payment of $1.5 billion or higher. The fine ultimately imposed totaled $2.2 billion.
In August 2012, Johnson & Johnson agreed to pay $181 million to 36 U.S. states in order to settle claims that it had promoted risperidone for off-label uses including for dementia, anger management, and anxiety.
The medical profession need to confess for their sins
The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotic treatment to avoid acute withdrawal syndrome or rapid relapse. Some have argued the additional somatic and psychiatric symptoms associated with dopaminergic super-sensitivity, including dyskinesia and acute psychosis, are common features of withdrawal in individuals treated with neuroleptics. This has led some to suggest the withdrawal process might itself be schizomimetic, producing schizophrenia-like symptoms even in previously healthy patients, indicating a possible pharmacological origin of mental illness in a yet unknown percentage of patients currently and previously treated with antipsychotics. This question is unresolved and remains a highly controversial issue among professionals in the medical and mental health communities, as well the public.