Neurochemistry

– Multiple per cell forming arbors, non/spiny; clustered near soma; highly plastic
– Organise, respond, synthesise inputs to neuron

nucleus contains the DNA (DNA the same in every nucleus).. Chromatin determines cell expression ie. what gene is what

DNA transcribed to mRNA
mRNA moves to cytoplasm
in the ribosome –> aminio acids
in the rough ER –.> protein

phospholipid bilayer (impermeable to water)

transmembrane spanning proteins allow for communication

Hydrophilic messengers cannot cross the cell membrane.

• Electrical to chemical to electrical signalling

(if only electrical will just be excited – epilepsy)

• Conversion of AP to Ca2+ influx
-Calcium leaks in –> fusion of vesicles to membrane –> exocytosis

• Colocalisation of neurotransmitters (Dale’s law)

• Biogenic amines
– Acetylcholine, adrenaline, dopamine,
histamine, noradrenaline, serotonin
• Amino acids
– Excitatory: glutamate, aspartate
– Inhibitory: GABA, glycine
• Purines
– ATP, adenosine

– Opioids: 20 peptides
• Endorphins from pre-proopiomelanocortin
• Enkephalins from pre-proenkephalin A
• Dynorphins from pre-prodynorphin
–
Neurohypophyseal
• Oxytocin, vasopressin
– Pituitary releasing hormones
• CRF, TRF, Somatostatin, GHRF
– Others – Substance P, CCK, VIP, NPY

mediated by glutamate and GABA
magnesium blocks pore, when things bind – change shape and Mg displaced

Influx of NA = depolarisation = AP = excitatory (glutamate)

GABA –> Cl- –> hypopolarises

– 10-1 to 101 seconds, intracellular messengers
• Long-term (gene expression, protein
synthesis)
– Minutes to weeks

Initiation:
A drug or stimulus acts on a given target protein and causes an acute drug effect, with repeated administration perturbations in the target protein occur

Adaptation
Overtime and with continue administration adaptive changes in the neurons containing the target protein occurs
Adaptive changes in these neurons leads to changes in their neuronal circuitry that are stable and having lasting effects
Fundamentally psychotropic drugs bring about their effects by interfering with neurotransmission

Repeated agonist exposure desensitises receptors
Repeated antagonist exposure sensitises receptors

5 subunits (pentamic ) usually comprising of 2α ,2β, 1γ

BZD binds to α and γ

They constitute a large family of receptors from many hormones and slow transmitters

They are membrane receptors that are coupled to intracellular effector systems via a G-protein which is attached to the cytoplasmic side of the membrane and functions like a switch

They are made or a single poly peptide chain threaded back and forth resulting in 7 transmembrane α helices (4 extracellular and 3 intracellular domains)

The N terminal domain is intracellular whereas the C- terminal domain is extracellular (false = opposite)

GPTase activity is associated with the α subunit of the G-protein.

G proteins can activate / deactivate ion channels

1. Adenylate cyclase
2. cyclic AMP
3. Protein kinase A –> into cell nucleus and can turn on or off gene expression through chromatic. CREB —> transcription

nb. lithium increases IP3

One neuron one neurotransmitter (exception rather than the rule)

eg. BDNF
tyrosine kinase becomes phosphorylated – come together

adaptation and chronic changes

dual serotonin and norepinephrine reuptake inhibition (venlafaxine);
serotonin-2 antagonism/reuptake inhibition (nefazodone);
a2 antagonism plus serotonin-2 and -3 antagonism (mirtazapine).
The selective norepinephrine and dopamine reuptake inhibitor bupropion defines a novel class of antidepressant that has no direct actions on the serotonin system.”