Neurotransmitters are endogenous chemicals that enable neurotransmission. It is a type of chemical messenger which transmits signals across a chemical synapse, such as a neuromuscular junction, from one neuron to another "target" neuron, muscle cell, or gland cell. Neurotransmitters are released from synaptic vesicles in synapses into the synaptic cleft, where they are received by neurotransmitter receptors on the target cells. Many neurotransmitters are synthesized from simple and plentiful precursors such as amino acids, which are readily available from the diet and only require a small number of biosynthetic steps for conversion. Neurotransmitters play a major role in shaping everyday life and functions. Their exact numbers are unknown, but more than 200 chemical messengers have been uniquely identified.
Psychopharmacology is the scientific study of the effects drugs have on mood, sensation, thinking, and behavior. It is distinguished from neuropsychopharmacology, which emphasizes the correlation between drug-induced changes in the functioning of cells in the nervous system and changes in consciousness and behavior.
The raphe nuclei are a moderate-size cluster of nuclei found in the brain stem. They have 5-HT1 receptors which are coupled with Gi/Go protein inhibiting adenyl cyclase. They function as autoreceptors in brain and decreases release of serotonin. The antianxiety drug Buspirone act as partial agonist. Selective serotonin reuptake inhibitor (SSRI) antidepressants are believed to act in these nuclei, as well as at their targets.
The periaqueductal gray is a nucleus that plays a critical role in autonomic function, motivated behavior and behavioural responses to threatening stimuli. PAG is also the primary control center for descending pain modulation. It has enkephalin-producing cells that suppress pain.
The reticular formation is a set of interconnected nuclei that are located throughout the brainstem. The reticular formation is not anatomically well defined because it includes neurons located in different parts of the brain. The neurons of the reticular formation make up a complex set of networks in the core of the brainstem that extend from the upper part of the midbrain to the lower part of the medulla oblongata. The reticular formation includes ascending pathways to the cortex in the ascending reticular activating system (ARAS) and descending pathways to the spinal cord via the reticulospinal tracts of the descending reticular formation.
Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. This is in contrast to synaptic transmission in which an axonal terminal secretes neurotransmitters to target fast-acting receptors of only one particular partner neuron. Neuromodulators are neurotransmitters that diffuse through neural tissue to affect slow-acting receptors of many neurons. Major neuromodulators in the central nervous system include dopamine, serotonin, acetylcholine, histamine, and norepinephrine. Neuromodulators are known to have modulatory effects on target areas such as decorrelation of spiking, increase of firing rate, sharpening of spatial tuning curves, maintenance of increased spiking during working memory.
The nucleus raphe pallidus receives afferent connections from the periaqueductal gray, the Paraventricular nucleus of hypothalamus, central nucleus of the amygdala, lateral hypothalamic area, and parvocellular reticular nucleus.
The dorsal raphe nucleus is located on the midline of the brainstem and is one of the raphe nuclei. It has rostral and caudal subdivisions.
The nucleus raphe magnus, is located directly rostral to the nucleus raphe obscurus, and receives input from the spinal cord and cerebellum.
The lateral hypothalamus(LH), also called the lateral hypothalamic area, contains the primary orexinergic nucleus within the hypothalamus that widely projects throughout the nervous system; this system of neurons mediates an array of cognitive and physical processes, such as promoting feeding behavior and arousal, reducing pain perception, and regulating body temperature, digestive functions, and blood pressure, among many others. Clinically significant disorders that involve dysfunctions of the orexinergic projection system include narcolepsy, motility disorders or functional gastrointestinal disorders involving visceral hypersensitivity, and eating disorders.
The 5-HT3 receptor belongs to the Cys-loop superfamily of ligand-gated ion channels (LGICs) and therefore differs structurally and functionally from all other 5-HT receptors (5-hydroxytryptamine, or serotonin) receptors which are G protein-coupled receptors. This ion channel is cation-selective and mediates neuronal depolarization and excitation within the central and peripheral nervous systems.
Desmetramadol (INN), also known as O-desmethyltramadol (O-DSMT), is an opioid analgesic and the main active metabolite of tramadol. Tramadol is demethylated by the liver enzyme CYP2D6 in the same way as codeine, and so similarly to the variation in effects seen with codeine, individuals who have a less active form of CYP2D6 will tend to get reduced analgesic effects from tramadol. This also results in a ceiling effect which limits tramadol's range of therapeutic benefits to the treatment of moderate pain.
The 5-HT2C receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). It is a G protein-coupled receptor (GPCR) that is coupled to Gq/G11 and mediates excitatory neurotransmission. HTR2C denotes the human gene encoding for the receptor, that in humans is located at the X chromosome. As males have one copy of the gene and in females one of the two copies of the gene is repressed, polymorphisms at this receptor can affect the two sexes to differing extent.
The serotonin 1A receptor is a subtype of serotonin receptor that binds the neurotransmitter serotonin. It is a G protein-coupled receptor (GPCR), coupled to the Gi protein, that mediates inhibitory neurotransmission. The serotonin 1A receptor is encoded by the HTR1A gene.
TCB-2 is a hallucinogen discovered in 2006 by Thomas McLean working in the lab of David Nichols at Purdue University where it was named 2C-BCB. It is a conformationally-restricted derivative of the phenethylamine 2C-B, also a hallucinogen, and acts as a potent agonist for the 5-HT2A and 5-HT2C receptors with a Ki of 0.26 nM at the human 5-HT2A receptor. In drug-substitution experiments in rats, TCB-2 was found to be of similar potency to both LSD and Br-DFLY, ranking it among the most potent phenethylamine hallucinogens yet discovered. This high potency and selectivity has made TCB-2 useful for distinguishing 5-HT2A mediated responses from those produced by other similar receptors. TCB-2 has similar but not identical effects in animals to related phenethylamine hallucinogens such as DOI, and has been used for studying how the function of the 5-HT2A receptor differs from that of other serotonin receptors in a number of animal models, such as studies of cocaine addiction and neuropathic pain.
SB-216641 is a drug which is a selective antagonist for the serotonin receptor 5-HT1B, with around 25x selectivity over the closely related 5-HT1D receptor. It is used in scientific research, and has demonstrated anxiolytic effects in animal studies.
The rostral ventromedial medulla (RVM), or ventromedial nucleus of the spinal cord, is a group of neurons located close to the midline on the floor of the medulla oblongata (myelencephalon). The rostral ventromedial medulla sends descending inhibitory and excitatory fibers to the dorsal horn spinal cord neurons. There are 3 categories of neurons in the RVM: on-cells, off-cells, and neutral cells. They are characterized by their response to nociceptive input. Off-cells show a transitory decrease in firing rate right before a nociceptive reflex, and are theorized to be inhibitory. Activation of off-cells, either by morphine or by any other means, results in antinociception. On-cells show a burst of activity immediately preceding nociceptive input, and are theorized to be contributing to the excitatory drive. Neutral cells show no response to nociceptive input.
Mefway is a serotonin 5-HT1A receptor antagonist used in medical research, usually in the form of mefway (18F) as a positron emission tomography (PET) radiotracer.
LP-44 is a drug which acts as a potent and selective agonist at the 5HT7 serotonin receptor. While LP-44 is less selective than the related compound LP-12, it has been more widely used in research and has been used to show the complex role of 5-HT7 receptors in several aspects of brain function, including regulation of the sleep-wake cycle and roles in stress, learning and memory.
