Introduction to CNS pharmacology Flashcards
organization of the CNS (outer to inner)
cortex: sensory/motor/thought process
limbic system: emotion/memory
diencephalon: endocrine/autonomic
cerebellum: sensory/motor coordination
midbrain: reflex pathways/infromation relay/ awareness/arousal
spinal cord: sensory/motor/autonomic
types of neurons
interneurons - communicate within the same brain region
projection neurons - axons project from one brain region to another
how do neurodegenerative diseases arise in the CNS
from loss/imbalance of neurons in neurotransmission - drugs attempt to restore balance
types of CNS neurotransmitters
- amino acids: glutamate, GABA
- acetylcholine
- monoamines: dopamine, norepinephrine, seretonin
- peptides
amino acid neurotransmitters
glutamate: excitatory at NMDA receptor (cause neurons to fire more)
GABA: inhibitory at GABAa receptor (inhibit neurons from firing)
Glutamate characteristics
- relay neuron through the CNS
- agonist of NMDA and non-NMDA receptors
- excitatory effects
NMDA receptor
- ion channel - increases Ca2+, Na+ and K+
- agonist = glutamate
- antagonist = PCP (a hallucinogen)
- also has binding sites for glycine, polyamines and zinc
The NMDA receptor had modulatory sites for which drugs/molecules
PCP
glycine
Ketamine
GABA characteristics
- relay neuron throughout the CNS associated with behaviour
- agonist at GABAa (and b) receptors
- inhibitory effects
GABAa receptor
- ion channel - increases Cl- in cell (inhibitory)
- agonist = GABA
- has sites for barbiturates, benzodiazepine and general anesthetics
ACh in CNS pharmacology
- ACh is at interneuron associated with motor control
- ACh at projection neurons associated with learning memory and cognition (lost in Alzheimer’s)
- Agonist at M and N receptors
Norepinephrine in CNS pharmacology
- found throughout the CNS
- important in awareness, arousal and autonomic control
- some antidepresants increase NE
- agonist as a1, a2 and B1 receptors
characteristics of dopamine
- precurosor of NE
- in cortex responsible for motivation/emotion
- in limbic system responsible for mood/behaviour
- in midbrain responsible for motor control
- at D1 receptor increase cAMP, at D2 receptor decrease cAMP
characteristics of serotonin
- project from midbrain and brainstem throughout the brain
- role in behaviour, control of sleep, temperature, appetite and neuroendocrine function
- Agonist at 5-HT receptor
5-HT receptor
- all are G protein linked except 5-HT3 (ion channel)
- 5-HT1: inhibitory - decrease cAMP
- 5-HT2: excitatory - increase DAG and IP3
- main agonist = serotonin
- agonist at 5-HT2A = LSD
- antagonist at 5-HT2A = antipsychotics
access of drugs to the CNS (BBB)
- BBB consists of endothelial cells and astrocytes
- endothelial = blood component of BBB
- astrocytes = support cells in the CNS
- some drugs cannot pass though the BBB
- transport of drugs occurs via passove diffusion
common neurodegenerative disorders
Alzheimers = loss od cholenergic neurons
Parkinsons = loss of dopaminergic neurons
neurodegenerative disorders
- progressive loss of specific population of neurons determines symptoms
- no cures available
- drugs used to enhance communication between remaining neurons
- with severe neuron loss, some drugs no longer effective at treating symptoms
symptoms of Alzheimers
- progressive and irreversible memory loss (decreased cholinergic input to hippocampus)
- cognitive impairment (decreased cholinergic input to cortex)
Pathological changes in AD brain
- Neurofibrillary tangles = intracellular accumulation of twisted fibres of phosphorylated tau protein
- Plaques = extracellular deposits of beta-amyloid protein
Treatment of Alzheimers
- aimed at restoring neuron communication and improving symptoms
- AChE inhibitors (donepezil) are the drugs used
- easily enter CNS and inhibit breakdown of ACh
- effective for mild-moderate AD
- side effects same as peripheral acting AChE inhibitors
how Donepezil works in Alzheimers
- inhibits AChE so ACh is not degraded
- more ACh can bind to M receptors at cortex
- causes increased Ca2+ and leads to improved memory
