Dopamine is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% of the catecholamine content in the brain. 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. Neurotransmitters are synthesized in specific regions of the brain, but affect many regions systemically. 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.
Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace amine-associated receptor 1 (TAAR1) and inhibiting vesicular monoamine transporter 2 (VMAT2) in monoamine neurons. To a lesser extent, it also acts as a neurotransmitter in the human central nervous system. In mammals, phenethylamine is produced from the amino acid L-phenylalanine by the enzyme aromatic L-amino acid decarboxylase via enzymatic decarboxylation. In addition to its presence in mammals, phenethylamine is found in many other organisms and foods, such as chocolate, especially after microbial fermentation.
Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malignant syndrome, and, as an adjunct, type 2 diabetes.
A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopamine not absorbed by the postsynaptic neuron is blocked from re-entering the presynaptic neuron. This results in increased extracellular concentrations of dopamine and increase in dopaminergic neurotransmission.
Carbidopa (Lodosyn) is a drug given to people with Parkinson's disease in order to inhibit peripheral metabolism of levodopa. This property is significant in that it allows a greater proportion of administered levodopa to cross the blood–brain barrier for central nervous system effect, instead of being peripherally metabolised into substances unable to cross said barrier.
The vesicular monoamine transporter (VMAT) is a transport protein integrated into the membranes of synaptic vesicles of presynaptic neurons. It transports monoamine neurotransmitters – such as dopamine, serotonin, norepinephrine, epinephrine, and histamine – into the vesicles, which release the neurotransmitters into synapses as chemical messages to postsynaptic neurons. VMATs utilize a proton gradient generated by V-ATPases in vesicle membranes to power monoamine import.
Nomifensine is a norepinephrine-dopamine reuptake inhibitor, i.e. a drug that increases the amount of synaptic norepinephrine and dopamine available to receptors by blocking the dopamine and norepinephrine reuptake transporters. This is a mechanism of action shared by some recreational drugs like cocaine and the medication tametraline. Research showed that the (S)-isomer is responsible for activity.
Fencamfamin (INN), also known as fencamfamine or by the brand names Glucoenergan and Reactivan, is a stimulant which was developed by Merck in the 1960s.
Troparil is a stimulant drug used in scientific research. Troparil is a phenyltropane-based dopamine reuptake inhibitor (DRI) that is derived from methylecgonidine. Troparil is a few times more potent than cocaine as a dopamine reuptake inhibitor, but is less potent as a serotonin reuptake inhibitor, and has a duration spanning a few times longer, since the phenyl ring is directly connected to the tropane ring through a non-hydrolyzable carbon-carbon bond. The lack of an ester linkage removes the local anesthetic action from the drug, so troparil is a pure stimulant. This change in activity also makes troparil slightly less cardiotoxic than cocaine. The most commonly used form of troparil is the tartrate salt, but the hydrochloride and naphthalenedisulfonate salts are also available, as well as the free base.
(–)-2β-Carboisopropoxy-3β-(4-iodophenyl)tropane is a stimulant drug used in scientific research, which was developed in the early 1990s. RTI-121 is a phenyltropane based, highly selective dopamine reuptake inhibitor and is derived from methylecgonidine. RTI-121 is a potent and long-lasting stimulant, producing stimulant effects for more than 10 hours after a single dose in mice which would limit its potential uses in humans, as it might have significant abuse potential if used outside a medical setting. However RTI-121 occupies the dopamine transporter more slowly than cocaine, and so might have lower abuse potential than cocaine itself.
A reuptake inhibitor (RI) is a type of drug known as a reuptake modulator that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron. This leads to an increase in extracellular concentrations of the neurotransmitter and an increase in neurotransmission. Various drugs exert their psychological and physiological effects through reuptake inhibition, including many antidepressants and psychostimulants.
Deoxyepinephrine, also known by the common names N-methyldopamine and epinine, is an organic compound and natural product that is structurally related to the important neurotransmitters dopamine and epinephrine. All three of these compounds also belong to the catecholamine family. The pharmacology of epinine largely resembles that of its "parent", dopamine. Epinine has been found in plants, insects and animals. It is also of significance as the active metabolic breakdown product of the prodrug ibopamine, which has been used to treat congestive heart failure.
A dopamine releasing agent (DRA) is a type of drug which induces the release of dopamine in the body and/or brain. No selective DRAs are currently known. Many releasing agents of both dopamine and norepinephrine and of serotonin, norepinephrine, and dopamine are known, however. Serotonin–dopamine releasing agents are much rarer and are not selective for monoamine release. Examples of NDRAs include amphetamine and methamphetamine, and an example of an SNDRA is MDMA. The most selective dopamine releaser is 4-methylaminorex, but it also has considerable activity as a norepinephrine releaser. These drugs are frequently used for recreational purposes and encountered as drugs of abuse.
JNJ-7925476 is a triple reuptake inhibitor antidepressant discovered by Johnson & Johnson, but never marketed.
A reuptake enhancer (RE), also sometimes referred to as a reuptake activator, is a type of reuptake modulator which enhances the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron, leading to a decrease in the extracellular concentrations of the neurotransmitter and therefore a decrease in neurotransmission.
BeKm-1 is a toxin from the Central Asian scorpion Buthus eupeus. BeKm-1 acts by selectively inhibiting the human Ether-à-go-go Related Gene (hERG) channels, which are voltage gated potassium ion channels.
Bupicomide is a chemical compound created and manufactured by Lanospharma Laboratories Company, Ltd. It is used experimentally as a beta blocker and clinically as a strong vasodilator with the noted side effects of reduced systolic, diastolic and mean arterial pressure.
N,N-Dimethyldopamine (DMDA) is an organic compound belonging to the phenethylamine family. It is related structurally to the alkaloid epinine (N-methyldopamine) and to the major neurotransmitter dopamine. Because of its structural relationship to dopamine, DMDA has been the subject of a number of pharmacological investigations. DMDA has been detected in Acacia rigidula.
The vanilloids are compounds which possess a vanillyl group. They include vanillyl alcohol, vanillin, vanillic acid, acetovanillon, vanillylmandelic acid, homovanillic acid, capsaicin, etc. Isomers are the isovanilloids.
Kaitocephalin is a non-selective ionotropic glutamate receptor antagonist, meaning it blocks the action of the neurotransmitter glutamate. It is produced by the fungus Eupenicillium shearii. Although similar molecules have been produced synthetically, kaitocephalin is the only known naturally occurring glutamate receptor antagonist. There is some evidence that kaitocephalin can protect the brain and central nervous system, so it is said to have neuroprotective properties. Kaitocephalin protects neurons by inhibiting excitotoxicity, a mechanism which causes cell death by overloading neurons with glutamate. Because of this, it is of interest as a potential scaffold for drug development. Drugs based on kaitocephalin may be useful in treating neurological conditions, including Alzheimer's, amyotrophic lateral sclerosis (ALS), and stroke.
