Amphetamine is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. Amphetamine was discovered in 1887 and exists as two enantiomers: levoamphetamine and dextroamphetamine. Amphetamine properly refers to a specific chemical, the racemic free base, which is equal parts of the two enantiomers, levoamphetamine and dextroamphetamine, in their pure amine forms. The term is frequently used informally to refer to any combination of the enantiomers, or to either of them alone. Historically, it has been used to treat nasal congestion and depression. Amphetamine is also used as an athletic performance enhancer and cognitive enhancer, and recreationally as an aphrodisiac and euphoriant. It is a prescription drug in many countries, and unauthorized possession and distribution of amphetamine are often tightly controlled due to the significant health risks associated with recreational use.
Dopamine is an organic chemical of the catecholamine and phenethylamine families. It functions both as a hormone and a neurotransmitter, and plays several important roles in the brain and body. It is an amine synthesized by removing a carboxyl group from a molecule of its precursor chemical L-DOPA, which is synthesized in the brain and kidneys. Dopamine is also synthesized in plants and most animals. In the brain, dopamine functions as a neurotransmitter—a chemical released by neurons to send signals to other nerve cells. The brain includes several distinct dopamine pathways, one of which plays a major role in the motivational component of reward-motivated behavior. The anticipation of most types of rewards increases the level of dopamine in the brain, and many addictive drugs increase dopamine release or block its reuptake into neurons following release. Other brain dopamine pathways are involved in motor control and in controlling the release of various hormones. These pathways and cell groups form a dopamine system which is neuromodulatory.
Stimulants is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and invigorating, or drugs that have sympathomimetic effects. Stimulants are widely used throughout the world as prescription medicines as well as without a prescription as performance-enhancing or recreational drugs. The most frequently prescribed stimulants as of 2013 were lisdexamfetamine, methylphenidate, and amphetamine. It is estimated that the percentage of the population that has used amphetamine-type stimulants and cocaine combined is between 0.8% and 2.1%.
Methylphenidate, sold under the trade name Ritalin among others, is a stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is a first line medication for ADHD. It may be taken by mouth or applied to the skin. Different formulations have varying durations of effect.
The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmental area in the midbrain, to the ventral striatum of the basal ganglia in the forebrain. The ventral striatum includes the nucleus accumbens and the olfactory tubercle. The release of dopamine from the mesolimbic pathway into the nucleus accumbens regulates incentive salience and facilitates reinforcement and reward-related motor function learning; it may also play a role in the subjective perception of pleasure. The dysregulation of the mesolimbic pathway and its output neurons in the nucleus accumbens plays a significant role in the development and maintenance of an addiction.
Monoamine transporters (MATs) are protein structures that function as integral plasma-membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs are responsible for the reuptake of their associated amine neurotransmitters. MATs are located just outside the synaptic cleft (peri-synaptically), transporting monoamine transmitter overflow from the synaptic cleft back to the cytoplasm of the pre-synaptic neuron. MAT regulation generally occurs through phosphorylation and posttranslational modification. Due to their significance in neuronal signaling, MATs are commonly associated with drugs used to treat mental disorders as well as recreational drugs. Compounds targeting MATs range from medications such as the wide variety of tricyclic antidepressants, selective serotonin reuptake inhibitors such as fluoxetine (Prozac) to stimulant medications such as methylphenidate (Ritalin) and amphetamine in its many forms and derivatives methamphetamine (Desoxyn) and lisdexamfetamine (Vyvanse). Furthermore, drugs such as MDMA and natural alkaloids such as cocaine exert their effects in part by their interaction with MATs, by blocking the transporters from mopping up dopamine, serotonin, and other neurotransmitters from the synapse.
Dextroamphetamine is a central nervous system (CNS) stimulant and an amphetamine enantiomer that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance and cognitive enhancer, and recreationally as an aphrodisiac and euphoriant. Dextroamphetamine was also used in the past by some country's military forces to fight fatigue during extended combat operations.
The dopamine hypothesis of schizophrenia or the dopamine hypothesis of psychosis is a model that attributes symptoms of schizophrenia to a disturbed and hyperactive dopaminergic signal transduction. The model draws evidence from the observation that a large number of antipsychotics have dopamine-receptor antagonistic effects. The theory, however, does not posit dopamine overabundance as a complete explanation for schizophrenia. Rather, the overactivation of D2 receptors, specifically, is one effect of the global chemical synaptic dysregulation observed in this disorder.
Atomoxetine, sold under the brand name Strattera among others, is a medication used to treat attention deficit hyperactivity disorder (ADHD). It may be used alone or along with stimulants. Use is only recommended in those who are at least six years old. It is taken by mouth.
Adderall is a combination medication containing four salts of amphetamine. Adderall is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance enhancer and cognitive enhancer, and recreationally as an aphrodisiac and euphoriant. It is a central nervous system (CNS) stimulant of the phenethylamine class. By salt content, the active ingredients are 25% levoamphetamine salts and 75% dextroamphetamine salts.
Dopaminergic pathways, sometimes called dopaminergic projections, are the sets of projection neurons in the brain that synthesize and release the neurotransmitter dopamine. Individual neurons in these pathways are referred to as dopamine neurons. Dopamine neurons have axons that run the entire length of the pathway. The neurons' somata produce the enzymes that synthesize dopamine, and they are then transmitted via the projecting axons to their synaptic destinations, where most of the dopamine is produced. Dopaminergic nerve cell bodies in such areas as the substantia nigra pars compacta tend to be pigmented due to the presence of the black pigment melanin. Dopaminergic pathways are involved in many functions such as executive function, learning, reward, motivation, and neuroendocrine control. Dysfunction of these pathways and nuclei may be involved in multiple diseases and disorders such as Parkinson's disease, attention deficit hyperactivity disorder, addiction, and restless legs syndrome (RLS).
Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through different protein interactions. The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors.
The norepinephrine transporter (NET), also known as solute carrier family 6 member 2 (SLC6A2), is a protein that in humans is encoded by the SLC6A2 gene.
Trace amines are an endogenous group of trace amine-associated receptor 1 (TAAR1) agonists – and hence, monoaminergic neuromodulators – that are structurally and metabolically related to classical monoamine neurotransmitters. Compared to the classical monoamines, they are present in trace concentrations. They are distributed heterogeneously throughout the mammalian brain and peripheral nervous tissues and exhibit high rates of metabolism. Although they can be synthesized within parent monoamine neurotransmitter systems, there is evidence that suggests that some of them may comprise their own independent neurotransmitter systems.
Lisdexamfetamine, sold under the brand name Vyvanse among others, is a medication that is used to treat attention deficit hyperactivity disorder (ADHD) in people over the age of five as well as for moderate to severe binge eating disorder in adults. Lisdexamfetamine is taken by mouth. In the United Kingdom it is usually less preferred than methylphenidate. Its effects generally begin within 2 hours and last for up to 12 hours.
Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the TAAR1 gene. TAAR1 is an intracellular amine-activated Gs-coupled and Gq-coupled G protein-coupled receptor (GPCR) that is primarily expressed in several peripheral organs and cells, astrocytes, and in the intracellular milieu within the presynaptic plasma membrane of monoamine neurons in the central nervous system (CNS). TAAR1 was discovered in 2001 by two independent groups of investigators, Borowski et al. and Bunzow et al. TAAR1 is one of six functional human trace amine-associated receptors, which are so named for their ability to bind endogenous amines that occur in tissues at trace concentrations. TAAR1 plays a significant role in regulating neurotransmission in dopamine, norepinephrine, and serotonin neurons in the CNS; it also affects immune system and neuroimmune system function through different mechanisms.
Amfonelic acid is a research chemical and dopaminergic stimulant with antibiotic properties.
A norepinephrine–dopamine reuptake inhibitor (NDRI) is a drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine and dopamine by blocking the action of the norepinephrine transporter (NET) and the dopamine transporter (DAT), respectively. This in turn leads to increased extracellular concentrations of both norepinephrine and dopamine and, therefore, an increase in adrenergic and dopaminergic neurotransmission.
Inhibitory control, also known as response inhibition, is a cognitive process and more specifically, an executive function – that permits an individual to inhibit their impulses and natural, habitual, or dominant behavioral responses to stimuli in order to select a more appropriate behavior that is consistent with completing their goals. Self-control is an important aspect of inhibitory control. For example, successfully suppressing the natural behavioral response to eat cake when one is craving it while dieting requires the use of inhibitory control.
Dopamine therapy is the regulation of levels of the neurotransmitter dopamine through the use of either agonists, or antagonists; and has been used in the treatment of disorders characterized by a dopamine imbalance. Dopamine replacement therapy (DRT) is an effective treatment for patients suffering from decreased levels of dopamine. Often dopamine agonists, compounds that activate dopamine receptors in the absence of that receptor's physiological ligand, the neurotransmitter dopamine, are used in this therapy. DRT has been shown to reduce symptoms and increase lifespan for patients suffering from Parkinson’s Disease. Dopamine regulation plays a critical role in human mental and physical health. The neurons that contain the neurotransmitter are clustered in the midbrain region in an area called the substantia nigra. In Parkinson's patients, the death of dopamine-transmitting neurons in this area leads to abnormal nerve-firing patterns that cause motor problems. Research in patients with schizophrenia indicates abnormalities in dopamine receptor structure and function.
