Neuro Chemistry

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neurochemistry
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focuses on the basic chemical composition and processes of the nervous system
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neuropharmacology
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is the study of compounds that selectively affect the nervous system
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EP or adrenaline
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chemical messenger that acts as a hormone to mobilize the body for fight or flight during times of stress and as a NT in the CNS
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NE or noradrenaline
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NT found in the brain and in the PNS
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ligands
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fit receptors exactly and activate or block them
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endogenous ligands
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NT and hormones NT: chemical released by a neuron onto a target with an excitatory or inhibitory effect outside the CNS many of these chemicals circulate in the blood stream as hormones
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exogenous ligands
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drugs and toxins from outside the body
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Synthesis and storage of NT
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_ in the axon terminal–building blocks from food are pumped into cell via transporters (protein molecules embedded within the cell membrane) _ in the cell body according to instruction contained in the DNA, transported on microtubules to axon terminal
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NT release
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at the terminal the action potential opens voltage sensitive Ca2+ channels, Ca2+ enters the terminal and binds to the protein calmodulin forming a complex complex causes some vesicles into empty the synapse and others get ready to empty their contents
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receptor-site activation
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after being released, the NT must diffuse across the synapse and activates receptors on the postsynaptic membrane autoreceptors–“self-receptor” on the presynaptic membrane that responds to the transmitter that the neuron releases
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inotropic receptor
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embedded membrane protein with 2 parts–a binding site for a NT and a pore that regulates ion flow to directly and rapidly change membrane voltage
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metabotropic receptor
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embedded membrane protein with a binding site for a NT but no pore linked to a G protein that can affect other receptors or act with second messengers to affect other cellular processes
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G protein
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belongs to a family of guanyl-nucleotide-binding proteins coupled to meatbotropic receptors that, when activated bind to other proteins
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second messenger
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a chemical that carries a message to initiate a biochemical process activated by a NT
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up regulation
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is an increase in the number of receptors
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down regulation
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is a decrease in the number of receptors
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deactivation of the NT
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diffusion away from synaptic cleft degradation by enzymes in the synaptic cleft reuptake into the presynaptic neuron for subsequent re-use taken up by neighboring glial cells *not mutually exclusive
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type I synapses
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excitatory typically located on dendrites round vesicles dense material on membranes wide cleft large active zone
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type II synapses
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inhibitory typically located on cell body flat vesicles sparse material on membranes narrow cleft small active zone
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criteria for identifying neurotransmitters
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the chemical must be synthesized in the neuron or otherwise be present in it when the neuron is active the chemical must be released and produce a response in a target the same responses must be obtained when the chemical is experimentally placed on the target a mechanism must exist for removing the chemical from its site of action after its work is done
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small molecules transmitters
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class of quick acting NT synthesized from dietary nutrients and packaged ready for use in axon terminals ex.: ACh, DA, NE,EP, Glu, GABA, Gly, histamine
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tyrosine hydroxylase
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rate-limiting factory _ restricts the rate at which all the catecholamines can by synthesized
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amino acid transmitters
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glutamate-main excitatory transmitter GABA-main inhibitory transmitter
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glutamate
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main excitatory transmitter cannot pass blood-brain barrier–synthesized within the cell using glutamine released by glial cells, glial cells take up released glutamate and transform to glutamine
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neuropeptide
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a multifunctional chain of amino acids that act as a NT synthesized from mRNA on instructions from the cell’s DNA do not bind to ion channels; do not have direct effects on the voltage of the postsynaptic membrane, act indirectly via G-protein coupled receptors
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transmitter gases
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synthesized in cell as needed easily crosses cell membrane support metabolic processes
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activating system
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pathway that coordinates activity through a single NT
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somatic nervous system
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cholinergic
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cholinergic neuron
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neuron that uses ACh as its main NT excites skeletal muscles to cause contractions ACh produced in nuclei in midbrain and basal forebrain
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autonomic NS
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cholinergic neurons from the CNS control both divisions both NE and ACh have excitatory effects on some organs and inhibitory effects on others
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CNS
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cholinergic dopaminergic x2 noradrenergic serotonergic cell bodies are located in a nucleus in the brainstem and their axons are distributed through a wide region of the brain
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cholinergic system
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involved in attention, memory maintaining neuronal excitability–helps maintain working electroencephalographic pattern Alzheimer’s disease–linked to decreased ACh synthesis, treated with acetylcholinesterase inhibitors
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dopaminergic system
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mesostriatal–originates in substantia nigra, projects to striatum, maintaining normal motor behavior parkinson’s disease treated with L-dopa mesolimbocortial–originates in ventral tegmentum, projects to nucleus accumbens, basal forebrain, frontal cortex, reward, motivation, addiction increased DA= schizophrenia decreased DA= ADHD, treat with DA stimulants
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noradgrenergic system
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originates in locus coeruleus, projects throughout cortex emotion decreased NE= major depression increased NE= mania
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serotonergic system
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originate in raphe nuclei, project throughout brain maintaining wakefulness learning increased 5-HT= OCD decreased 5-HT= depression abnormalities in brainstem 5-HT neurons linked to sleep apnea and SIDS
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blood brain barrier
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endothelial cells of the brain capillaries are surrounded by the end feet of astrocytes attached to the capillary wall, covering about 80% of it glial cells provide a route for the exchange of food and waste between capillaries and the brain’s extracellular fluid
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agonists
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substance that enhances the effectiveness of a NT
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antagonist
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substance that blocks/decreases the effectiveness of a NT
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drug action at synapses
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drugs can alter chemical processes at any of the seven major stages of synaptic transmission–synthesis, storage, release, receptor interaction, inactivation, reuptake, degradation
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inverse agonists
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bind to receptor and initiates opposite effect of usual transmitter
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competitive ligands
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bind to the same part of receptor molecule as endogenous ligand
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noncompetitive ligand
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bind to modulatory sites that are not part of the receptor complex that normally binds the transmitter
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efficacy
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is that ability of a bound ligand to activate the receptor partial agonists produce a medium response regardless of dose
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dose-response curve, ED50
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is a graph of the relationship between drug doses and the effects the does ate which the drug shows half of its maximal effect is the _ a drug that has comparable effects at lower doses is more potent
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therapeutic index
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is the separation between the effective does and a toxic one drugs with wider _ are safer
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tolerance
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decrease in response to a drug with the passage of time
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metabolic tolerance
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organ systems become more effective at eliminating the drug, increase in number of enzymes used to break down substance
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functional tolerance
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target tissues show altered sensitivity to the drug activities of brain cells adjust to minimize effects of the substance
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cross tolerance
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response to a novel drug is reduced because of tolerance developed in response to a related drug suggests that the two drugs affect a common nervous system target
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anxiolytics
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or tranquilizers are depressants–drugs that reduce nervous system activity GABA benzodiaxepines–antianxiety agents barbiturates–produce sedation and sleep, also general anesthesia, coma, death dissociate anesthetics–group of sedative-hypnotics developed as anesthetics, produce altered states and hallucinations (GHB, ketamine, date rape drugs) alcohol–similar neurochemical effects as barbiturates, GABAa receptors and increases inhibitory effect, also stimulates dopamine pathways causing euphoric effects, chronic use causes liver damage and thiamine deficiency
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antipsychotic agents
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first generation–major tranquilizer, drug that blocks D2 dopamine receptor, reduce the positive symptoms of schizophrenia, produce symptoms of parkinson’s disease second generation-weakly block D2 receptors but also block serotonin 5-HT2 receptors, reduce negative symptoms, affect motivation and reduce agitation but may result in weight gain
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dopamine hypothesis of schizophrenia
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proposal that schizophrenia symptoms are due to excess activity of the NT _ evidence–antipsychotic drugs block D2 receptors, amphetamine promotes release of _ and can produce symptoms similar to schizophrenia
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antidepressants
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MAO inhibitors–block the enzyme MAO from degrading NT such as dopamine, NE, and 5-HT tricyclic _–first generation _ with a chemical structure characterized by 3 rings that block 5-HT reuptake transporter proteins second-generation _–action is similar to first generation but is more selective, SSRIs, block the reuptake of serotonin into the presynaptic terminal
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mood stabilizers
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used to treat bipolar disorder mutes the intensity of one pole of the disorder thus making the other pole less likely to recur mechanism is not well understood–lithium may increase serotonin release, valproate may stimulate GABA activity
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opioid
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compound that binds to a group of brain receptors also sensitive to morphine 2 natural sources– opium used for thousands of years to produce euphoria, analgesia, sleep, and relief from diarrhea and coughing, the brain–peptides in the body that have opioid like effects are collectively called endorphins
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endorphin
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peptide hormone that acts on a NT and may be associated with feelings of pain or pleasure 3 classes–endomorphins, enkephalins, dynorphins
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opioid analgesic
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drugs with sleep-inducing and pain-relieving properties codeine morphine some synthetic _ prescribed for clinical use in pain management are hydromorphone, levorphanol, methadone competitive inhibitors can be used to treat opioid addiction after the person has recovered from withdrawal symptoms–nalorphine and nalozone _ ingestion produces relaxation, sleep, euphoria, constipation, respiratory depression, decreased blood pressure, pupil constriction, hypothermia
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heroin
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an opiate drug synthesized from morphine more fat soluble and penetrates the BBB faster than morphine, therefore produces very rapid pain relief
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psychotropics
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behavioral stimulants affect motor activity and mood psychedelic and hallucinogenic stimulants affect perception and produce hallucinations general stimulants mainly affect mood
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behavioral stimulants
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increase motor behavior and elevate a person’s mood and level of alertness rapid administration of _ is most likely to be associated with addiction
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cocaine
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obtained from the leaves of the coca plant blocks dopamin reuptake powder is snorted or injected derivates such as novocaine are used as local anesthetics–reduce cell’s permeability to Na+ thereby reducing nerve conduction
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amphetamine
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dopamine agonist–blocks dopamine reuptake transporter, leaving more dopamine available at the synaptic cleft, stimulates release of dopamine from presynaptic membrane both mechanisms increase the amount of DA available in synapses to stimulate DA receptors some uses–initially an asthma treatment, study aid, improvement of alertness and productivity, weight-loss aid
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methamphetamine
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relatively inexpensive, yet potentially devastating neurotoxic–causes brain damage with prolonged use, damages both DA and 5HT neurons
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general stimulatns
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drugs that cause a general increase in the metabolic activity of cells caffeine–inhibits the enzyme that normally breaks down the second messenger cyclic AMP, increase in cAMP leads to an increase in glucose production within cells, which makes more energy available and allows for higher rates of cellular activity, blocks the effect of adenosine an endogenous neuromodulator that normally inhibits catecholamine release
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psychedelics
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alter sensory perception and cognitive processes and can produce hallucinations ACh- atropine, nicotine NE- mescaline HT5- LSD, psilocybin, ecstacy Anandimide- THC Glutamate- PCP, ketamine
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hallucinogens
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LSD, mescaline, magic muschrooms have visual effects have diverse neural action including those on NE, HT5, ACh and opiate systems many have potential clinical uses for treatment of mental health disorders–OCD, anxiety, depression, PTSD
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ACh psychedelics
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either block or facilitate transmission of ACh synapses nicotine–increases heart rate, blood pressure, hydrocholiric acid secretion, and bowel activity, acts as an agonist on nicotinic ACh receptors in the body and brain, rewarding effects are mediated by receptors in ventral tegmnetal area
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NE psychedelics
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mescaline produces pronounced psychic alterations, including a sense of spatial boundlessness and visual hallucinations
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serotonin psychedelics
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LSD and psilocybin stimulate some HT5 receptors ecstasy elevates _ concentrations by blocking reuptake and stimulating release chronic use can cause depression, memory disturbances and alters the structure and function of _ neurons
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endocannabinoids
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homologs of marijuanna produced in the brain–acts as retrograde messengers and may influence NT release from the presynaptic neuron
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Anandomine psychedelics
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alters memory formation, stimulates appetite, reduces pain sensitivity, protects from excitotoxic brain damage, lowers blood pressure, combats nausea, lowers eye pressure from glaucoma 2 cannabinoid receptors (metabotropic)– CB1 only in the CNS, CB2 prominent in the immune system
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glutamate psychedelics
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PCP and ketamine can produce hallucinations and out of body experiences they exert part of their action by blocking glutamate NMDA receptors involved in learning many _ like substances kill neurons–influx of Ca2+ into the cell which through second messengers activates a suicide gene leading to apoptosis
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drugs that
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