Glutamate and GABA

what is physostigmine?

AChE inhibitor that crosses the BBB

what does physostigmine cause?

confusion, hallucination, and coma

what cannot be used to treat myasthenia gravis?

physostigmine

why do drugs with central targets have side effects?

due to peripheral action

do nicotinic receptors have the same sequence?

they have different sequences

basal forebrain system

nucleus basilis of Meynert» substantia innominata»septal nucleus»cortex and hippocampus

what is the basal forebrain system involved in?

cognitive functions like memory

tegmental nuclei in pons

pons»VTA, brainstem, and thalamus

what is the tegmental nuclei in the pons involved in?

reward, arousal, and sleep/waking

scopolamine

a muscarinic antagonist

what does scopolamine induce?

amnesia, sometimes used during labor

how is Alheimers’s disease characterized?

amnesia and loss of cholinergic neurons

what is used to treat Alzheimers?

AChE inhibitors that cross the BBB(ex:donepezil)

common name for donepezil

Aricept

cerebral atrophy which accompanies Alzheimers?

narrow gyri and wide sulci, especially in frontal and temporal lobes

what lobes are the main target of cholinergic neurons?

frontal and temporal

why are cigarettes addictive if they dont act of dopamine or endorphins?

there are receptors for nicotine on VTA cells that release DA

Vesamicol

depletes ACh by inhibiting vesicular uptake

Black widow spider venom

stimulates ACh release

Botulinum toxin

inhibits ACh release

Hemicholinium-3

depletes ACh by inhibiting choline uptake by the nerve terminal

physostigmine

centrally acting reversible AChE inhibitor hat increases ACh level

Donepezil, Rivastigmine, and Galantamine

AChE inhibitors used in the treatment of Alzheimers disease

Neostigmine and pyridostigmine

peripherally acting reversible AChE inhibitors used in the treatment of Myasthenia gravis

sarin and soman

irreversible AChE inhibitors used as nerve gas agents

nicotine

stimulates nicotinic receptors(agonist)

succinylcholine

nicotinic receptor agonist that causes depolarization block

mecamylamine and D-tubocurarine

block nicotinic receptors(antagonists)

muscarine, pilocarpine, and arecoline

stimulate muscarininc receptors(agonists)

atropine and scopolamine

block muscarinic receptors(antagonists)

what effects do GABA antagonists have?

sedative effects

what does glutamate have a special role in?

learning and memory

Glutamate synthesis

Glutamine»Glutaminase»Glutamate

where are glutamate transporters and receptors found?

glutaminergic cells, astrocytes, post-synaptic cells at tripartite synapses

glutamate excitotoxicity

excessive levels of glutamate elevate intracellular calcium too much, which leads to programmed cell death

are glutamate receptors ionotropic or metabotropic?

both; 3 ionotropic, 8 metabotropic

3 ionotropic glutamate receptors

AMPA, Kainate, NMDA

which of the ionotropic glutamate receptors allows for calcium entry?

NMDA

what do NMDA receptors require to open?

glutamate and a coagonist(glycine of D-serine)

what ion blocks NMDA receptors?

Magnesium ions, but the block is removed by depolarization of the inside of the cell

AP5(APV)

acts as a competitve antagonist on the glutamate binding site

DO PCP, Ketamine, and MK-801 block at the same site at APV?

block at a different site

is PCP a (non)competitive (ant)agonist?

noncompetitive antagonist

ionotropc receptors

ligand-gated ion channels

multiple aspects to ion channels

selectivity, conductance, modification through intracellular phosphorylation

example of drug that decreases channel conductance

PCP and ketamine block the pore in NMDA glutamate receptors

example of how conductance can be increased

phosphorylation of the AMPA subtype of glutamate receptor can increase channel conductance

what increases the amount of phosphorylation of the AMPA receptor?

amphetamine

why are cows having seizures?

low magnesium causes overactivity of NMDA receptors

what blocks AMPA and kainate thus reducing seizures?

NBQX

what can ketamine treate?

seizures(NMDA receptors)

what is coincidence detection?

feature of NMDA receptors which is thought to underlie LTP involved in learning

the entry of NA through AMPA receptors allows for what to enter?

Ca2+

calcium entry effects

recruiting more AMPA receptors to be inserted into the post synaptic membrane, can strengthen synapses by increasing # of AMPA receptors during LTP

if there are more AMPA receptors then…?

there are larger efects when glutamate is released

what can increase AMPA conductance?

phosphorylation

what enhances glutamate release?

nitric oxide

what serves as retrograde messengers?

gaseous and lipid neurotransmitters