Introduction to pharmacology of the CNS Flashcards
what type of receptors do acetylcholine, dopamine and noradrenaline used?
any exceptions?
what type of affect do they have?
they all use metabotropic receptors
only exception is the 5HT3 receptor which is ionotropic
they have mixed effects
what type of effects do the peptide neurotransmitters have?
opioid NT - inhibitory
NPY - excitatory
list some of the problems associated with drugs of the CNS
measurement and assessment of disorder
- not really applicable for epilepsy
multiple receptors
cellular tolerance
- most CNS conditions are chronic, so require prolonged drug use, but receptors can be dynamic
side effects:
- numerous and hinder compliance
drug delivery:
- problem with crossing the blood - brain barrier
particularly with peptide based drugs
neuronal circuitry
- e.g. inhibition leading to disinhibition
co-existence of peptides
how are peptides different from the normal neurotransmitters
they’re produced in precursor form, and processed en - route (they’ve slow axonal transport)
they’re not re-uptaken, but broken down by peptidases
in active neurones, if synthesis lags behind release - depletion occurs
peptide can be broken down by peptidases, and thereby diffuse into other cells further from cell that released them:
- thus they have important effects at distant sites
- volume transmission is very important
the type of peptides produced from the same gene, is very important on external factors
what are opioid receptors involved in? what can they cause?
receptors:
- anxiety
- pain
- dependance
indication in:
- chronic pain
- addiciton
what are tachykinin functions? what is their possible indication?
function:
- inflammation
- anxiolysis
indication:
- headache
- anxiety
what are CCK functions? what is their possible indication
function
- axiogenesis
- satiation
- dopamine function
- pain
indication:
- PD
- eating disorders
- physcosis
what are NPY function? what is their possible indication?
function:
obesity
mood
indication:
- eating disorder
- depression
- epilepsy
what is the function of vasopressin? what are the possible indication?
function:
- learning and memory
indication:
- amnesia
what is the function of somatostatin? what are the possible indications?
function:
- analgesia
indication:
pain
what are the functions of Galanin? what are the possible indications?
function
- sensory transmission
- feeding
indication:
- pain
- eating disorder
most neurotransmitters are amino acid derivatives, what are the exceptions?
acetylcholine
cannabinoids
adenosine
NO
what type of vesicles are involved in
- fast neuronal transmission
- slow peptide transmission
- slow synaptic transmission
small, synaptic vesicles
- large dense core synaptic vesicles
- small dense core synaptic vesicles
what are the GCPRs of the Gi type coupled to?
what toxin acts on this receptor
negatively coupled to AC
pertusis
what are the GCPRs of the Gs type coupled to
what toxin acts on this receptor
positively coupled to AC
cholera toxins
what are the GCPRs of the Gq type coupled to
positively coupled to PLCb
what are the roles of glutamate?
what receptors is it coupled to?
glutamate is coupled to post-synpatic receptors: NMDA AND AMPA
it is coupled to pre-synpatic receptors which are slow metabotropic
and kainaite receptors
involved in:
- LTP (memory)
- delayed hyperexciation
- neuronal development
- epilepsy
- neuronal death
- point - point transmission
- pain wind up in the spinal cord
- neuromodulation (through the GCPRs)
what are the metabotropic receptors of glutamate linked to?
so the metabotropic receptors can either be positively or negatively linked
Gi receptors: which are negatively coupled to AC
or Gq receptors: which are positively coupled to PLC
- the only one linked to this is mGLU R1/5 - this one is the positively linked one
what pathologies are the NDMA receptors involved in? and how?
recall they’re also involved in development of the visual system and LTP in hippocampus
pain transmission (wind up) - due to amplification and prolongation of impulses cell death - due to excessive calcium influx - alzheimer's - PD? - cerebral ischameia
epilepsy
explain how the NMDA receptor work?
both voltage and ligand gated
ligand required:
- glutamate and glycine
voltage gated:
- at physiological range, the gates are blocked from the inside by magnesium
- depolarisation, removes the magnesium
means:
- receptor not active at physiological range
- delayed in action, because required prior depolarisation
what two calcium channel types are involved in pre-synpatic transmission
N and P calcium channel types
explain wind up pain and LTP?
what nerve fibres are involved
LTP: long lasting enhancement of signal transmission between two neurones, even after neuronal firing is inactivated
it occurs when:
- high stimulation of C-nerve fibres occurs, causing a high rate of C fibre depolarisation
- this prior depolarisation activates NMDA receptors
- activation of NMDA receptor causes increase in the response to the same stimuli over a long period of time
this only occurs in C fibres
what are the two types of GABA receptors? how are they different?
how can the function of GABA receptors be modulated using two different classes of drugs?
GABA a - fast ionotropic - uses Cl- channels
GABA b - slow ionotropic - uses potassium and calcium channels
GABA receptors:
- allosteric modulation of GABAa receptors via benzodiazpenes, increasing the receptor affinity to GABA
- barbiturates: those hold open the Cl- channels of the receptors
what is glycine?
what antagonist is its sensitive to?
peripherial equivalent of GABA
sensitive to strychnine as an antagonist
