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  • Catecholamines (Dopamine, Norepinephrine, Epinephrine), Indolamines (Serotonin)

 Amino Acid

  • GABA, Glutamate, Glycine, Aspartate

Peptides (examples)

s: enkephalins, Neurohypophyseals: vasopressin, oxytocin, Secretins: corticotropin-releasing factor, Insulins: insulin, insulin growth factors, substance P

 Acetylcholine (ACh)

  1. In CNS and brain, influences alertness, attention, and memory
  2. Formed by combination of acetyl CoA + choline (enzyme choline acetyltransferase)
  3. Does not undergo reuptake; action is terminated by cholinesterase
  4. Found in:
    1. Neuro-muscular junction
    2. Post ganglionic parasympathetic nerve endings
    3. All preganglionic nerve endings of ANS
    4. Some of the post ganglionic neurons of sympathetic N.S
    5. Large pyramidal cells (BETZ CELLS) of motor cortex
    6. By many different neurons in basal ganglia:
      1. Two receptor types: Nicotonic (movement) Muscarinic (autonomic)
      2. Mysthenia Gravis characterized by defect in Ach transmission.
      3. Botulinum toxin prevents release of Ach; Black widow spider venom stimulates release; Curare blocks Ach nicotine receptors

 Serotonin (5-HT, or 5-hydroxytryptamine)

  1. Behavioral effects are complex
  2. Plays a role in regulation of mood; control of eating, sleep, and arousal; and pain
  3. Raphe Nuclei (in brainstem) à entire CNS
  4. Tricyclic antidepressants (eg, imipramine,) block both Serotonin and NE uptake


 Dopamine (DA)

  1. Generally associated w/ motor disorders and neuropsychiatric problems (schizophrenia, ADHD, tics), as well as modulation of reward centre.
  2. Conditions due to defects in dopamine synthesis include PKU, Parkinson’s
  3. Excessive dopamine produced by coke, amphetamine, L-dopa; can lead to visual hallucinations, hyperkinetic movement disorders
  4. Midbrain (substantia nigra pars compacta and ventral tegmental) à striatum, prefrontal, limbic, amygdala. 3 well-known pathways:
    1. Nigrostriatal – major component of extrapyramidal motor system; decreased DA here causes rigidity, tremor, and akinesia; excess causes dyskinesia
    2. Mesolimbic – probably propagates positive symptoms of psychosis; rewarding effects of certain stimuli including drugs; ventral tegmental areas (midbrain) to amygdala/limbic
    3. Mesocortical – probably propagates some negative symptoms of psychosis; planning, strategy preparation; ventral tegmental to frontal cortex.
  5. Dopamine has 5 receptor.  D1& D5 act by increasing cAMP (via adenylyl cyclase) & D2,D3 & D4 act by decreasing cAMP
  6. Phenyalanine à tyrosine à DOPA à Dopamine (tyrosine hydroxylase rate-limiting)
  7. Terminate process: reuptake, monoamine oxidase (MAO), etc.

 Norepinephrine (NE) (noradrenalin)

  • Functions helps regulate mood, memory, hormones, blood flow, and motor behavior
  • Also thought to increase vigilance; role in sexual behavior and control of appetite
  • Locus Ceruleus (pons) à entire CNS
  • Tricyclic antidepressants (eg, imipramine, clomipramine) block both Serotonin and NE uptake

 Epinephrine (adrenalin)

  1. Hormone produced by adrenal medulla
  2. Also produced in brain, but minor importance compared with NE
  3. Stimulates sympathetic division of ANS to produce “flight or fight”



GABA   Cell bodies in entire CNS project to entire CNS

  • Principal inhibitory transmitter substance in brain.
  • Synthesised from glutamic acid through the activity of glutamic acid decarboxylase (GAD) is used as marker of GABA secreting neurons
  • On GABA A receptors – acts by increasing Cl- conductance
  • On GABA B receptors- increasing K+ efflux, mediator for presynaptic inhibition
  • Enhanced activity produces sedative, anxiolytic, and anticonvulsant effects


  • Glutamate   Cell bodies in entire CNS project to entire CNS
  • Principal excitatory transmitter (along with aspartate) substance in brain and cord
  • Implicated in neural plasticity, learning, and memory
  • Four types of glutamate receptors, once being the NMDA receptor



Glycine   Inhibitory neurotransmitter in spinal cord and lower brain

  1. May play a modulatory role at interneurons in cord
  2. acts by increasing Cl- conductance
  3. Blocked by strychnine


  • Project to entire CNS; no mechanism for reuptake once released; deactivated by enzymes
  • Substance P – mediator of inflammation, carrying pain signals(Tachykinins)
  • Vasopressin facilitate water reabsorption by kidneys; may play a role in memory consolidation
  • Somatostatin – modulation of heat, pain, sleep; also reduced in cortex of Alz pts
  • Angiotensin II- central actions include stimulation of pressor responses and drinking
  • Opoids (Enkephalin)- pain perception, stress, respiratory regulation, temperature control

μ (mu)

k (kappa)


  (k+ conductance)                    

(Closes Ca2+ channels)

Ca2+ channel close      





Resp depression
















1.  Tachykinins are peptides that excite neurons, evoke behavioral responses, are potent vasodilators and contract (directly or indirectly) many smooth muscles.Until now, only three tachykinins have been isolated and sequenced from mammalian tissues: SP, NKA (neuromedin L, neurokinin, and substance K), and NKB (neurokinin and neuromedin k). Substance P is found in high concentration in the endings of primary afferent neurons in the spinal cord, and it is probably the mediator at the first synapse in the pathways for slow pain, is responsible for the axon reflex. In the intestine, it is involved in peristalsis.

2.  Orexins, also called hypocretins, are the common names given to a pair of excitatory neuropeptide hormones (Orexin-A and B). Produced by lateral and posterior hypothalamus. The orexin/hypocretin system is involved in the stimulation of food intake. In addition, it stimulates wakefulness and energy expenditure. People lacking the orexin/hypocretin neuropeptide itself also have narcolepsy.

3.  Neurotrophins  are proteins necessary for survival and growth of neurons. Some of these neurotrophins are products of the muscles or other structures that the neurons innervate, but others are produced by astrocytes. These proteins bind to receptors at the endings of a neuron. They are internalized and then transported by retrograde transport to the neuronal cell body, where they foster the production of proteins associated with neuronal development, growth, and survival.They have trk receptors which dimerizes, and this initiates autophosphorylation in the cytoplasmic tyrosine kinase domains of the receptors.




Nerve growth factor (NGF)

trk A

Brain-derived neurotrophic factor (BDNF)

trk B

Neurotrophin 3 (NT-3)

trk C, less on trk A and trk B

Neurotrophin 4/5 (NT-4/5)

trk B

Schwann cells and astrocytes produce
ciliary neurotropic factor (CNTF). This factor promotes the survival of damaged and embryonic spinal cord neurons and may prove to be of value in treating human diseases in which motor neurons degenerate.


NOTE: Autoimmunity to GAD appears to cause the stiff-man syndrome (SMS), a disease characterized by fluctuating but progressive muscle rigidity and painful muscle spasms, presumably due to GABA deficiency.


GABA is formed by decarboxylation of glutamate. The enzyme that catalyzes this reaction is glutamate decarboxylase (GAD), which is present in nerve endings in many parts of the brain. GABA is metabolized primarily by transamination to succinic semialdehyde and thence to succinate in the citric acid cycle. GABA transaminase (GABA-T) is the enzyme that catalyzes the transamination. Pyridoxal phosphate, a derivative of the B complex vitamin pyridoxine, is a cofactor for GAD and GABA-T.

SYNAPSE: Junction between two neurons, where information from one neuron is transmitted or relayed to another neuron, but there is no protoplasmic connection between the two neurons.


  1. AXO-DENDRITIC (Most common)

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