Modafinil, like other stimulants, increases the release of monoamines – specifically, the catecholamines norepinephrine and dopamine – from the synaptic terminals. However, modafinil also elevates histamine levels. Which is one of the differences between it and amphetamines. Modafinil has also been the target of studies, identifying effects on dopamine in the striatum and nucleus accumbens, noradrenaline in the hypothalamus and serotonin in the Amygdala and frontal cortex.
Your Brain and What It Does
---AMYGDALA: Lying deep in the center of the limbic emotional brain, this powerful structure, the size and shape of an almond, is constantly alert to the needs of basic survival including sex, emotional reactions such as anger and fear. Consequently it inspires aversive cues, such as sweaty palms, and has recently been associated with a range of mental conditions including depression to even autism. It is larger in male brains, often enlarged in the brains of sociopaths and it shrinks in the elderly.
-BRAIN STEM: The part of the brain that connects to the spinal cord. The brain stem controls functions basic to the survival of all animals, such as heart rate, breathing, digesting foods, and sleeping. It is the lowest, most primitive area of the human brain.
CEREBELLUM: Two peach-size mounds of folded tissue located at the top of the brain stem, the cerebellum is the guru of skilled, coordinated movement (e.g., returning a tennis serve or throwing a slider down and in) and is involved in some learning pathways.
-CEREBRUM: This is the largest brain structure in humans and accounts for about two-thirds of the brain’s mass. It is divided into two sides — the left and right hemispheres—that are separated by a deep groove down the center from the back of the brain to the forehead. These two halves are connected by long neuron branches called the corpus callosum which is relatively larger in women’s brains than in men’s. The cerebrum is positioned over and around most other brain structures, and its four lobes are specialized by function but are richly connected. The outer 3 millimeters of “gray matter” is the cerebral cortex which consists of closely packed neurons that control most of our body functions, including the mysterious state of consciousness, the senses, the body’s motor skills, reasoning and language.
-The Frontal Lobe is the most recently-evolved part of the brain and the last to develop in young adulthood. It’s dorso-lateral prefrontal circuit is the brain’s top executive. It organizes responses to complex problems, plans steps to an objective, searches memory for relevant experience, adapts strategies to accommodate new data, guides behavior with verbal skills and houses working memory. Its orbitofrontal circuit manages emotional impulses in socially appropriate ways for productive behaviors including empathy, altruism, interpretation of facial expressions. Stroke in this area typically releases foul language and fatuous behavior patterns.
-The Temporal Lobe controls memory storage area, emotion, hearing, and, on the left side, language.
-The Parietal Lobe receives and processes sensory information from the body including calculating location and speed of objects.
The Occipital Lobe processes visual data and routes it to other parts of the brain for identification and storage.
-HIPPOCAMPUS: located deep within the brain, it processes new memories for long-term storage. If you didn't have it, you couldn't live in the present, you'd be stuck in the past of old memories. It is among the first functions to falter in Alzheimer's.
-HYPOTHALAMUS: Located at the base of the brain where signals from the brain and the body’s hormonal system interact, the hypothalamus maintains the body’s status quo. It monitors numerous bodily functions such as blood pressure and body temperature, as well as controlling body weight and appetite.
-THALAMUS: Located at the top of the brain stem, the Thalamus acts as a two-way relay station, sorting, processing, and directing signals from the spinal cord and mid-brain structures up to the cerebrum, and, conversely, from the cerebrum down the spinal cord to the nervous system.http://www.brainwaves.com/ "Recently, modafinil was screened at a large panel of receptors and transporters in an attempt to elucidate its pharmacology. Of the sites tested, it was found to significantly act only on the dopamine transporter (DAT), inhibiting the reuptake of dopamine with an IC50 value of 4 μM. Accordingly, it produces locomotor activity and extracellular dopamine concentrations in a manner similar to the selective dopamine reuptake inhibitor (DRI) vanoxerine, and blocks methamphetamine-induced dopamine release. As a result, it seems that modafinil exerts its effects by acting as a weak DRI, though it cannot be ruled out that other mechanisms may also be at play. On account of its action as a DRI and lack of abuse potential, modafinil was suggested as a treatment for methamphetamine addiction by the authors of the study.http://en.wikipedia.org/wiki/Modafinil. Fundamental differences in modafinil vs. amphetaminehttp://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSumhttp://www.sciencedirect.com/science...6452298000153t
Amphetamines increase the release of monoamines throughout the brain. Provigil both increases the release of monoamines and histamine levels more specifically in the hypothalamus.
The specific monoamines increased by Provigil are dopamine in the striatum and nucleus accumbens, noradrenaline in the hypothalamus and ventrolateral preoptic nucleus, and serotonin in the amygdala and frontal cortex. Amphetamines increase the levels of norepinephrine, serotonin, and dopamine (in the nigrostriatal region- is a neural pathway that connects the substantia nigra with the striatum. It is one of the four major dopamine pathways in the brain region of the brain)inducing euphoria and with a strongly addictive potential:
Amphetamines are a competitive inhibitor of DA. Attaching directly to DA substrate binding sites on DAT. It creates a twofold action
1)- Blocking the reuptake of DA into the neuron.
2)- And at an even more profound level, actually entering the neuron itself. Thus separating the amphetamines m.o. a much more robust class from the allosteric reuptake inhibitors. Once inside the actual cell amphetamine then competitively inhibits DA at the VMAT. Now the function of storing DA into the synaptic vesicles is reversed causing displacement of DA . Building in the front neuronal vesicles until the cell is forced to release the DA back into the synapse by opening a new ion channel. At the same time the DAT cycle is now reversed and instead of releasing the DA into the neuron. It is now pumping it back into the synaptic cleft. Dexamphetamine has a higher proclivity for DAT. While adderall is more inclined to bind to NET. Both affect the two monoamines and release large active amounts of DA and NE into the synapse for use. And draining the cells of the normal levels of both to a high degree. Note, the spanules or xr release of these amps. do not have the same commando type of actions. Even though the pharmacological function is similar. The drugs aggressive actions are slowed significantly and lower the addiction potential, neurotoxicity, and systematic overload in the brain.
Modafinil and its big brother, armodafinil also bind to DAT. Modafinil's lower affinity for binding to DAT, is made up for by its naturally high plasma levels. It's effect on the increase of synaptic DA leads to a tonic firing and a downstream effects on the neurotransmitters histamine and
orexin/hypocretin. The pharmacokinetics suggest the success of its stimulating qualities are also due in part to its slow rise in plasma. The sustained plasma levels of 6-8 hrs reinforcing the tonic DA activity to promote wakefulness. Instead of a phasic DA activity that promotes reinforcement and abuse.. Armodafinil is the active R enantiomer minus the S. Armodafinil has even later times for peak levels, a longer half-life, and higher plasma levels, 6-14 hrs.
The future of stimulants and cognitive enhancers
THE AVAILABILITY AND PORTRAYAL OF STIMULANTS OVER THE INTERNET
Ty S. Schepis, Ph.D.,1 Douglas B. Marlowe, J.D., Ph.D.,2,3 and Robert F. Forman, Ph.D.2,3,4http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386963/
The Future of Psychopharmacological Enhancements:
Expectations and Policies