S U B S TA N C E P

• Neurotransmitter Type: Neuropeptide (specifically Brain-Gut)

• Precursors: 11 amino acid chain (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met) synthesized via preprotachykinin A gene
• Receptors: Neurokinin 1 or NK-1R (G-protein coupled receptor)
• Postsynaptic Effects: Excitatory (often seen in conjunction w/ glutamate)
• Synapse Removal: Inactivated via peptidases to form amino acid fragments
• Location: Hippocampus, Neocortex, GI Tract, & Spinal Cord
• General Functions:
• Most often associated w/ detecting pain & changes in temperature in the PNS

• Also plays roles in mood, vomiting, inflammation, vasodilation, & cell and vessel growth

• Receptor Types:
• Also called tachykinin receptor 1 (TACR1) made of 7 hydrophobic transmembrane domains

• Located in the CNS & the PNS

• Can be compromised by diseases like asthma, rheumatoid arthritis, & ailments in the GI tract

• Research Article: Substance P & COVID-19

• Substance P is enhanced in COVID-19 patients causing an increased inflammatory response

• Can be responsible for many of the adverse symptoms observed (especially those seen in critically ill patients)

• Reducing levels of SP could yield very positive outcomes for these patients
Acetylcholine
Neurotransmitter Type: Small molecule

Precursors: Choline(catalyzed by ChAT, choline acetyltransferase)+acetyl CoA(synthesized from glucose)

Receptors: AChR(2 types: nicotinic/muscarinic)

Postsynaptic Effects: Excitatory

Synapse Removal:cholinergic synapses, neuromuscular junctions, AChE(acetylcholinesterase), acetate and choline

Location: Synapses in ganglia of visceral motor system , CNS, as well as the parasympathetic nervous system

General Functions: Depending on the type of receptor and location the effects of ACh can vary. In parasympathetic
neurons where ACh will bind to muscarinic receptors this neurotransmitter controls secretion, HR, and breathing. In
cholinergic neurons where ACh binds to nicotinic receptors it will control memory, motor function, and
neurotransmission.

Receptor Types: Nicotinic Receptor; ligand-gated ion channel(large protein complex composed of 5 subunits)
Muscarinic Receptor; activated by muscarine, metatropic controls most effects of ACh in the brain, binding on the
extracellular surface of the receptor, causes a conformational change for binding of-protein.
G

Research Article: Acetylcholine and the complex interdependence of memory and attention
- ScienceDirect
By Rachel Han
ATP (as a neurotransmitter)
-Type: Small molecule NT
- Precursors: ADP, AMP
- Location: PNS (motor neurons of spinal cord, sensory
and autonomic ganglia) & CNS (dorsal horn &
hippocampal neurons
- Postsynaptic Effects: Excitatory
-General function(s): co-transmitter; autonomic control, crosses membrane twice, 3 subunits req.
sensory transduction, synaptic modulation, and
communication with glial cells.
-Synapse Removal: enzymatic degradation to
adenosine & AMP ( also signals but not a classic NT)
-enzymes include apyrase, ecto-5’ nucleotidase,
nucleoside transporters
Adenosine triphosphate | Neurology
-3 classes of purinergic receptors: P2X receptors
(iono) and 2 classes of G-protein (meta)
-P2X receptors mediate excitatory postsynaptic
responses, widely distributed in neurons.
->in sensory nerves, mechanosensation and pain,
unknown elsewhere
->unique structure bc transmembrane domain only
-1 G-protein class sensitive to adenosine and other to
ATP; both found throughout brain, and peripheral
tissues
-Research: ATP increases quantal fraction of
catecholamine but not vesicular content- increases its
release fusion pore opening- in chromaffin cells(make
neurohormones) https://baylor.primo.exlibrisgroup.com/permalink/01BUL_INST/122ppak/cdi_swepub_prima
ry_oai_gup_ub_gu_se_281530
BRAIN DERIVED NEUROTROPHIC FACTOR (BDNF)
Hannah Vedder, Baylor University
Transmitter Type, Precursors, and Synaptic
Removal
BDNF is a protein. It is initially synthesized as
preproBDNF, before it is converted to proBDNF and
eventually mature BDNF by proteases. BDNF is
removed from the synapse by enzymatic degration
and proteolytic cleavage. BDNF and proBDNF are
both active signaling molecules and work largely along
the same pathways.
Article Summary
BDNF helps protect from mood disorders because it upregulates long term
potentiation, hippocampal neurogenesis, survival, plasticity, connectivity, and
function. Because of this, low levels of BDNF & mutations in the genes that
code it have been shown to come with higher risk of depression. BDNF may
eventually be able to serve as a biomarker of depression.
Levels of BDNF can be increased by chronic physical activity (clinically,
16kcal/kg/week). Because of this, exercise, in combination with
antidepressants and other treatments, can be an effective treatment for mood
disorders.

Transmitter Effects and Receptors

BDNF has both excitatory and inhibitory post-synaptic
effect, and it is involved in the regulation of dendritic
growth and differentiation, and can also play a role
in receptor mediated neuronal apoptosis. BDNF and
proBDNF act on two types of receptors—TrkB and
p75. Both types of receptors are expressed in both the
CNS and PNS. The p75 receptor is a supportive
receptor that mediates neuronal death and dendritic
pruning, and the TrkB is an RTK which mediates
https://doi.org/10.1155/2017/7260130
dendritic growth. https://www.hindawi.com/journals/np/2017/7260130/
 CORTICOTROPHIN RELEASING FACTOR (CRF)
• Neurotransmitter Type: Neuropeptide
• Precursor: Inactivated CRH gene
• Synthesized in the ER and transported to the neuronal cytoplasm

• Receptors: CRF-1 (hippocampus) and CRF-2 (less common)

• Both are GCPRs in the anterior lobe of the pituitary gland

• Excitatory
• Synaptic Removal: diffusion throughout the body; also metabolized in the kidneys and liver
• Location: primarily in the hippocampus, pyramidal neurons, neuroendocrine cells in the amygdala, the paraventricular nucleus,
and the hypothalamus
• Function: Released in response to stress (fight/flight system)  increases fear, alertness, decreases appetite
• Regulates catecholamine synthesis/release from the adrenal gland, increases fear
• Also activates the HPA in response to stress (CRF  ACTH  cortisol)

• https://www.frontiersin.org/articles/10.3389/fncel.2019.00290/full
• CRF-1 receptor antagonists were used to reduce depressive like symptoms in mice because it blocked the release of CRF which
decreased the stress response. There were few side effects compared to other anti-depressants.
 Dopamine
By: Roland Martinez

● Neurotransmitter Type: Small Molecule NT (Biogenic Amine)

● Precursors: DOPA (DOPA decarboxylase)
● Receptors: Acts exclusively on G-protein-coupled receptors (Dopamine Receptors, D1-D5)
● Postsynaptic Effects: Both excitatory and inhibitory (Most dopamine receptor subtypes either activate or inhibit
adenylyl cyclase)
● Synapses Removal: Reuptake by Na+ dependent dopamine co-transporter (DAT), Degradation by monoamine oxidase
(MAO) and Catechol O-methyltransferase (COMT)
● Location: CNS neurons
○ Corpus striatum: major dopamine-containing area of the brain (present in several brain regions)
○ Receives major input from the substantia nigra
● General Functions: Coordination of body movements as well as motivation, reward, and reinforcement.
● Info. about receptor types:
○ VMAT (vesicular monoamine transporter): Loads and sends dopamine into vesicles
○ Dopamine Receptors (Dopaminergic receptors)
■ D1 and D5 receptors: Linked to stimulatory (excitatory) G-proteins that activate adenylate cyclase
■ D2, D3, and D4 receptors: Linked to inhibitory G-proteins that inhibit adenylate cyclase
● Research Article: “Dopamine Receptor-Specific Contributions to the Computation of Value”
○ Dopamine thought to play large role in value-based decision making
○ Test how the balance between D1 and D2 receptor subtypes influence value computation during risky decision
making.
○ D2 receptor blockade resulted in increased high risk high reward options
○ https://pubmed.ncbi.nlm.nih.gov/29251282/
ENDOCANNABINOIDS
Definition:
Kaitlyn Schmieder

Family of related endogenous signals that interact with cannabinoid receptors. These cannabinoid receptors are the same receptors that
are activated by cannabinoids such as THC, which is the active ingredient in Cannabis Sativa . Importantly, the endocannabinoid system is active in your body
regardless of whether you use marijuana, because it’s important for many bodily functions.
Type: Small molecule, unconventional neurotransmitters. Like the classical neurotransmitters, they are involved in neural communication and their release
is regulated by calcium, but they are not stored in vesicles or released in a traditional manner from the presynaptic terminal. The two main endocannabinoids
that we know of are anandamide and 2-arachidonylglycerol (2-AG). They are unsaturated fatty acids with polar head groups.
Precursors: Present in the lipid membrane and include a family of glycerophospholipids called NArPEs.
Synthesis: Stimulated by a second messenger in the postsynaptic cell that causes an increase in calcium ion concentration. Synthesized on demand.
Release: Signals can diffuse through the postsynaptic membrane due to their hydrophobic quality to reach cannabinoid receptors on other cells.
Receptors: Two main types of cannabinoid receptors called CB1 and CB2. Both are G-protein coupled receptors. Most research focuses on the CB1
receptors because they are most prevalent in the CNS, but more recent research focuses on the role of CB2 receptors in the immune system.
Postsynaptic Effects: Powerful influence on synaptic transmission because they can regulate neural communication via retrograde
transmission. After traveling backward from the postsynaptic cell, they bind to a receptor on the presynaptic cell. This activation inhibits calcium channels,
activates potassium channels, and interferes with vesicle release, and the result is an inhibition of presynaptic GABA or glutamate release. In this way,
depolarization of the postsynaptic neuron reduces synaptic transmission.
Location: Primary locations of CB1 receptors are the hippocampus and the cerebellum, which explains the difficulties with both memory and
coordination that marijuana users experience. CB1 receptors also found in the substantia nigra and caudate putamen, which are areas implicated in drug abuse.
Functions: Pain reduction, relaxing, eating, sleeping, and forgetting. Rodent studies show that they also play a role in memory and emotion regulation.
Research: Endocannabinoid system is implicated in anxiety and essential for forgetting avoidance behaviors that underlie anxiety.
Micale, Vincenzo; Stepan, Jens; Jurik, Anjela; et al. ( July 2017). Extinction of avoidance behavior by safety learning depends on endocannabinoid signaling in the
hippocampus. Journal of Psychiatric Research, 90 (3), 46-59.
Endorphins
● Neuropeptides
● Precursor peptide proopiomelanocortin forms α, β, and γ-
endorphins
● Bind to μ and 𝛿𝛿 opioid receptors throughout the brain, spinal cord,
and peripheral nervous system
○ Metabotropic receptors that us e G-proteins to open K+ channels and
clos e Ca 2 + channels
○ Reduces membrane excitability and s low s the firing of action potentials
● Reduces feelings of pain by inhibiting pain signaling pathw ays
● Released during exercise (runner’s high), eating, laughing, and
volunteering
● Receptors most dense at thalamus, periaqueductal gray, raphe
nuclei, spinal cord
● Also believed to function in rew ard, motor coordination, feeding
● ‘Naltrexone Blocks Endorphins Released w hen Dancing in
Synchrony’:
○ Naltrexone increas ed s ens itivity to pain w hile control group increas ed
their pain thres hold due to the releas e of endorphins
○ https ://link.s pringer.com/article/10.1007/s 40750-017-0067-y
 GABA (Gamma-aminobutyric acid)

Type/Location: Small molecule neurotransmitter; found throughout CNS, mostly in local circuit interneurons
Precursors: Glucose (sometimes pyruvate or glutamine)
TCA cycle Glutamic acid decarboxylase
Synthesis Glucose--------->Glutamate---------------------------->GABA
Receptors: GABA-A: ionotropic (Cl-); GABA-B: metabotropic: activates K+ channels or inhibits Ca2+ channels
Receptor effects: inhibitory (GABA-A occasionally excitatory when postsynaptic K+ levels high)
Research:
Schousboe, Arne. “Metabolic Signaling in the Brain and the Role of Astrocytes in Control of Glutamate and GABA Neurotransmission.”
Neuroscience Letters, Elsevier, 3 Feb. 2018, www.sciencedirect.com/science/article/pii/S0304394018300442.

Inactivation via reuptake through transporters on both presynaptic terminal and astrocytic membrane
GAT-1: presynaptic membrane
GAT-3: astrocytic membrane; can protect against seizures when inhibited
Astrocytes play a role in the glutamate-glutamine cycle
Uptake of both GABA and glutamate (more often glutamate)
TCA creates glutamate which is converted to glutamine
glutamine transported to presynaptic neuron to be converted to glutamate and then GABA
Glutamate as a Neurotransmitter
■ Type of NT: Small Molecule NT
■ Precursor: Alpha-Ketoglutarate (intermediate product in the citric-acid cycle) – Glutamine: in the Glutamate-
Glutamine Cycle.
■ Postsynaptic Effects: Excitatory
■ Receptors:
- Ionotropic: N-methyl-d-aspartate (NMDA), amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA),
and kainate receptor.
All three allow Na+ ions to flow into a postsynaptic neuron, depolarizing the neuron making it more
likely to fire an action potential. Specifically, NMDA receptors (often Ca2+ ions) have a unique characteristic that
allows them to be used in synaptic plasticity (synaptic changes that respond to experience). This is crucial for
learning and memory.
-Metabotropic: G-Coupled Proteins
■ Location: In both the CNS and PNS
■ Function: Glutamate is the most common neurotransmitter in both the central and the peripheral nervous
system. It is responsible for sending signals between nerve cells, and under normal conditions it plays an
important role in learning and memory.
■ Synapse Removal: The uptake into neurons and surrounding glial cells via specific transporters (EAATS) -the
Glutamate- Glutamine Cycle
■ Research: Analyzing metabotropic receptors from glutamate can be the key in treating neurological
disorders and chronic illness due to stress. https://pubmed.ncbi.nlm.nih.gov/30800054/
 Histamine
• Type: small-molecule neurotransmitter (a biogenic amine)
• Precursor: the amino acid histidine is acted on by L histidine decarboxylase to form histamine
• Post synaptic effects: excitatory
• Synapse Removal: both Histamine N-methyltransferase and MAO will help to break it down
• Receptors: all four histamine receptors are metabotropic and have 7 membrane spanning elements
• H1R: associated with the circadian rhythm, weird cycles of food intake and behavior. Also associated with long-term
potentiation
• H2R: associated with cognition and nociception
• H3R: acts as an auto receptor on tuberomammillary nucleus neurons, blocking this receptor increases amount of
neuronal histamine, ACh, DA thus improving cognition
• H4R: we don’t really know a lot about it or what it does
• Location: produced in the tuberomammillary nucleus (posterior hypothalamus) and acts in both the brain and spinal cord
• General Functions: maintenance of circadian rhythm, energy and endocrine homeostasis, sensory and motor function,
cognition, and attention
• Primary research article: looked at the relationship between food intake and amount of available histamine in the
circulation. They found that high levels of histamine were related to low voluntary intake of food and vice versa
(illustrating the role that histamine plays in food intake.
• Sources
• Haq, A., Bundrant, H., & Mercer, L. Food intake is inversely correlated with central nervous system histamine receptor (H1) concentrations in male Sprague-
Dawley rats fed normal, low protein, low energy or poor quality protein diets. The Journal of Nutrition, 126(12), 3083–3089.
https://doi.org/10.1093/jn/126.12.3083
• Helmut L. Haas, Olga A. Sergeeva, & Oliver Selbach. (2008). Histamine in the Nervous System. Physiological Reviews, 88(3), 1183–1241.
https://doi.org/10.1152/physrev.00043.2007
 Oxytocin
By Samantha Wieman
• Neurotransmitter Type: Peptide Hormone/Neuropeptide-can also act as NT
• Precursors: Synthesized as inactive precursor from OT gene
• Receptors: OTR (oxytocin receptor)- G-Protein Coupled Receptor
• Receptor Types: Only one- OTR. Responds to oxytocin to signal transduction
and activation of HPA
• Postsynaptic Effects: Excitatory
• Synapse Removal: As a neurotransmitter, its is degraded by peptidases. As a
hormone, it is metabolized in liver and kidneys
• Locations: Produced in hypothalamus and projects to the VTA, NAcc, and
amygdala and projects to the pituitary gland, which secrets it into bloodstream
• General Functions: Childbirth (uterine contraction during labor), breastfeeding
(milk let-down reflex), relationship building (trust/empathy)
• Research Article: Attachment in wound healing, PTSD, depression, and trauma.
Prevention of PTSD, increased resiliency, increased bonding
• Sharma, S. R., Gonda, X., Dome, P., & Tarazi, F. I. (2020). What’s Love Got to do with it: Role
of oxytocin in trauma, attachment and resilience. Pharmacology & Therapeutics, 214, N.PAG.
https://doi-org.ezproxy.baylor.edu/10.1016/j.pharmthera.2020.107602

https://www.youtube.com/watch?v=tLc9fQd58bg
 NITRIC OXIDE (NO)
NT CLASS: unconventional gaseous NT, radical nitrogenous species
NO SYNTHESIS: (e,n,i)NOS enzymes synthesize NO from arginine and citrulline
PHARMACODYNAMICS: Glu-NMDARs, GABAergic cerebellar purkinje cells, enteric nitrergic cells and guanylyl cyclase (GC)
PS ACTIONS: excitatory retrograde at Glu-NMDARs, inhibitory retrograde at GABAergic purkinje cells, excitatory anterograde at enteric nitrergic neurons
REMOVAL: diffusion across membrane, lasts less than 1 second in the synapse
LOCATION: eNOS expressed in endothelium, motor neurons and astrocytes, iNOS expressed in astrocytes and microglia, nNOS expressed in neurons, high density in HPA axis,
hippocampus and Glu-NMDARs

FUNCTIONS:
iNOS-CNS immunity via pathogen apoptosis by microglia
eNOS- major peripheral vasodilation circuit facilitated by GC/cGMP signaling and cerebral blood flow
nNOS-retrograde LTP circuit at the Glu-NMDARs, nNOS promotes Gastric motility via enteric nitrergic neuron synapses

NO RECEPTORS: psNOS enzymes nearby classical NT receptors, “retrograde co-transmission”

ARTICLE: “NMDARs and NO:cGMP Signaling Pathways Mediate Diazepam Induced Sensitization to Withdrawal in Mice.” -Telarek et al. 2017
• One group mice given daily Diazepam(3 wks), the other group dosed sporadically (given (GC, NMDAR, nNOS or NOS) antagonists, or L-Arg during free-period)
• Mice were injected with GABA-AR antagonist (Pentylenetrazole(PZ)) at the first sign of withdrawal(48 hrs after cessation) to induce seizures
• (GC, NMDAR, and nNOS) antagonists were effective in reducing PZ-induced seizures, implicating theses mechanisms in Diazepam tolerance and withdrawal
• DOI 10.1007/s12640-017-9810-1
 NOREPINEPHRINE
HUMAIRA ISLAM

• Type: Small Molecule NT

• Precursors: Dopamine (all catecholamines derived from tyrosine)
• Receptors: All GPCR
• ⍺1-adrenergic receptor: slow depolarization linked to inhibition of K+ channels
• ⍺2-adrenergic receptor: slow hyperpolarization due to activation of K+ channels
• β-adrenergic receptor: increases heart rate
• Post-Synaptic Effects: Excitatory
• Synapse Removal: Degraded by enzymes monoamine oxidase (MAO) and catechol-O-methyltransferase
(COMT) and by reuptake via norepinephrine transporter (NET)
• Location: CNS (locus coeruleus, limbic system, sympathetic ganglion cells); released from adrenal medulla (as
hormone)
• General Functions: linked to arousal, alertness, and attention; released in sympathetic nervous system and
involved with increased activity
• Research: Depletion of norepinephrine blocks VNS effects on cortical plasticity
• Daniel R. Hulsey, Christine M. Shedd, Sadmaan F. Sarker, Michael P. Kilgard, Seth A. Hays, Norepinephrine
and serotonin are required for vagus nerve stimulation directed cortical plasticity, Experimental
Neurology,Volume 320, 2019.
 Oxytocin
By Samantha Wieman
• Neurotransmitter Type: Peptide Hormone/Neuropeptide-can also act as NT
• Precursors: Synthesized as inactive precursor from OT gene
• Receptors: OTR (oxytocin receptor)- G-Protein Coupled Receptor
• Receptor Types: Only one- OTR. Responds to oxytocin to signal transduction
and activation of HPA
• Postsynaptic Effects: Excitatory
• Synapse Removal: Little is known but it is metabolized in liver and kidneys
• Locations: Produced in hypothalamus and sent to posterior pituitary gland-
secreted into bloodstream
• General Functions: Childbirth (uterine contraction during labor), breastfeeding
(milk let-down reflex), relationship building (trust/empathy)
• Research Article: Attachment in wound healing, PTSD, depression, and trauma.
Prevention of PTSD, increased resiliency, increased bonding
• Sharma, S. R., Gonda, X., Dome, P., & Tarazi, F. I. (2020). What’s Love Got to do with it: Role
of oxytocin in trauma, attachment and resilience. Pharmacology & Therapeutics, 214, N.PAG.
https://doi-org.ezproxy.baylor.edu/10.1016/j.pharmthera.2020.107602

https://www.youtube.com/watch?v=tLc9fQd58bg
 Serotonin
• Small-molecule (large, dense-core)
• Excitatory
• Derived from the amino acid tryptophan
• Taken up into neurons by a plasma membrane transporter and
hydroxylated in a reaction catalyzed by tryptophan-5-
hydroxylase (see figure 6.18B, p.134)
• Loading of 5-HT into synaptic vesicles via VMAT
• Acts upon 5-HT receptors
• Most Metabotropic / G-protein-coupled receptors
• 5-HT3 receptors – ligand-gated ion channels that are nonselective
to cations; mediate excitatory postsynaptic responses
• Impairment in receptor function leads to psychiatric disorders
• Removed from the synapse via a specific serotonin
transporter (SERT) in the presynaptic plasma
membrane
• primary catabolic pathway mediated by MAO
• Locations: primarily in groups of neurons in the raphe
regions of the pons and upper brainstem (with
widespread projections to the forebrain)
• Functions: circadian rhythms, motor behaviors,
emotional states, state of mental arousal
• SSRIs used to treat depression and anxiety (Prozac)
• LSD is an example of a drug that activates multiple 5-HT
receptors
• Activation of receptors decreases appetite and maintains
feelings of satisfaction (sometimes used to treat eating
disorders)
• Vlaev, I., Crockett, M. J., Clark, L., Müller, U., &
Robbins, T. W. (2017). Serotonin enhances the impact
of health information on food choice. Cognitive,
Affective & Behavioral Neuroscience, 17(3), 542–553.
https://doi-org.ezproxy.baylor.edu/10.3758/s13415-
016-0496-2
Enkephalins
• Neuropeptides
• An opioid peptide, related to
endorphins
• Regulate nociception and
inflammation
• Bind to opioid receptors (mu and
delta opioid receptors; metabotropic)
• 2 forms:
• Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu)
• Met-enkephalin (Tyr-Gly-Gly-Phe-Met)
• Precursor is pro-enkephalin
• Degraded by peptidases
• Found in many parts of the brain,
especially the basal ganglia
• Also produced by the adrenal medulla
and other peripheral tissues