What is GHB and how does it work? Flashcards
What is GHB?
A drug that is used as a date rape
What kind of receptor is GABAb?
A GPCR
How does the GABAb system work?
As a dimer (i.e. you need two of them activated to create an effect)
What are the two halves of the dimer that are required to carry out a signal?
- GABAb1
2. GABAb2
What is the function of the GABAb1 receptor?
The activator
What is the function of the GABAb2 receptor?
the signaller
Describe the cascade of GABAb?
GABAb acts on NMDA receptors
- Alpha subunit cleaves; the beta-gamma subunit goes on to negatively influence voltage-gated Ca2+ channels
- alpha subunit acts on Gi pathway (inhibits adenylyl cylcase from making cAMP from ATP)
- NMDA receptor has to be phosphorylated by protein kinase a to be activated
How does the GABAb receptor inhibit the NMDA receptor?
By preventing phosphorylation (therefore it inhibits the excitatory response)
What do presynaptic GABAb receptors prevent?
Ca2+ from causing vesicle to dock and release NTs
What does GHB stand for?
gamma hydroxybuterate
What is GHB synthesized from?
GABA
Describe the synthesis of GHB?
succinic semialdehide makes GHB from GABA
What does a low dose of GHB produce?
Excitement and euphoria (with some memory problems)
What is liquid X?
GHB at low doses (is paired with other club drugs)
What do moderate doses of GHB produce?
More memory problems and sedation
What do high doses of GHB produce?
coma and/or death
Why is GHB effective as a memory impairer in date rape situations (exam question)?
Because the LTP in NMDA receptors is blocked by the GABAb receptor cascade
What is an orphan receptor?
Proteins that act like receptors, but with no known ligand that specifically binds to it
What property can GHB have when it comes to neurotransmission (other than the possibility of it being its own neurotransmitter)?
GHB could be a GABAb co-signaller
What are monoamine neurotransmitters?
They are a class of compounds that have a single amine
What are the two classifications of monoamines?
Catecholamines and 5HTs
What are the catecholamine NTs?
- Dopamine (DA)
- Norepinephrine (NE)
- Epinephrine (Epi)
Is serotonin a catecholamine?
No, but it is a monoamine
What is the technical difference between epinephrine and adrenaline?
Epinephrine is used when referring to the effects in the CNS (i.e. in the brain) and adrenaline is used when referring to the effects in the PNS (i.e. in heart rate, pupil dilation, etc)
What is a rate limiting step?
The slowest step in the synthesis of a monoamine - this step determines how much is released, and how quickly more is synthesized
Describe the synthesis of dopamine.
- tyrosine gets into the brain via a BBB transporter
- tyrosine gets transformed into L-Dopa via tyrosine hydroxylase (TH)
- L-dopa gets transformed into dopamine via dopa decarboxylase
Describe the synthesis of norepinephrine.
- tyrosine gets into the brain via a BBB transporter
- tyrosine gets transformed into L-Dopa via tyrosine hydroxylase (TH)
- L-dopa gets transformed into dopamine via dopa decarboxylase
- dopamine gets transformed into norepinephrine via dopamine-beta-hydroxylase
Describe the synthesis of epinephrine
- tyrosine gets into the brain via a BBB transporter
- tyrosine gets transformed into L-Dopa via tyrosine hydroxylase (TH)
- L-dopa gets transformed into dopamine via dopa decarboxylase
- dopamine gets transformed into norepinephrine via dopamine-beta-hydroxylase
- norepinephrine gets transformed into epinephrine via phenylethanolamine-N-methyltransferase
What does impulse dependent mean?
That the substance is only effective when active firing of the neuron is occurring (for example, cocaine is impulse dependent, because it needs DA in order to enhance its signal)
What does impulse independent mean?
The neuron doesn’t have to fire for the substance to have an effect
- an example of an impulse independent substance would be meth
What effect do psychostimulants have?
They are indirect agonists that affect DA release
How is dopamine’s signal terminated?
- through reuptake (this is the primary method of signal termination) via DAT
- it is metabolized
Give some examples of medications that act on dopamine transporters.
- ADHD medication (ex. dexadrine, adderall, concerta)
- cocaine
- methamphetamine
How does ADHD medication affect neurotransmission?
These medications reverse the dopamine transporter DAT to instead push out more dopamine
How does cocaine affect neurotransmission?
It blocks the DA transporter (therefore it acts as an antagonist)
