CNS Depressants – Week 4 8/23/2013 2:23:00 PM
Quiz next week – starts 9am
Why use a CNS depressant? (class brainstorm)
E.g. valium, Xanax, ambien, rohypnol, GHB
Recreational (e.g. Xanax = happiness effects)
[Weaning for addiction] = valium there are more specific drugs for
Date rape (e.g. rohypnol)
[Schizophrenia] = valium there are more specific drugs for this
4 primary uses for CNS depressants:
o 1. To reduce anxiety
o 2. To facilitate sleep (i.e. sedative/counter insomnia)
o 3. To reduce awareness/consciousness
therapeutic = anesthesia
4. To reduce muscle spasms or associated pain
o Talked about last week Oral muscle relaxers (also CNS
1. To reduce stress:
What is anxiety?
Defined by dictionary =
o 1. Distress or uneasiness of mind
o 2. State of apprehension and psychic tension
It is essentially “nervous energy”
o Everyone experiences it…
What causes it?
o Anxiety is a natural response to certain situations
o Acuity it is ok to be anxious Some argue beneficial (when you are anxious it cognitively
primes you to do things such as study for exam or
something…it drives performance)
Can help memory…but when it goes on a long time it can
o Chronic anxiety becomes problematic
Get mood changes
Impairs memory (not good)
Get sick more
Irritability, pessimism, dysphoria, lack of concentration,
Drug that reduces it?
History of CNS depressants/anxiolytics:
CNS depressants have been used throughout civilization…
Can we think of any drugs that people have used to chill out and
o Psychedelics (e.g. scopolamine)
o Tobacco (e.g. nicotine)
o All of these give some contented euphoria
People have been using drugs for a long time to reduce stress
1850s – 2000s
What is a CNS depressant?
It‟s a drug that depressed your CNS activity
CNS functions to:
o 1. Receive info from PNS (the outside world)
o 2. Integrate and understand info
o 3. Initiate appropriate response
When you take a CNS depressant you start to decrease all of these
CNS and PNS systems work but talking to each other, neurons need to
be excitable these
Pharmacology angles for depressants: Decrease excitation – how?
o By dercrasing glutamatergic tone
Increase inhibition – how?
o By increasing GABAergic tone
o Main approach – CNS depressants by and large increase
GABAergic tone in the CNS
Glu and GABA:
You don‟t want too much inhibition or hyperexcitation
o It‟s a very fine balance that your brain has to try and keep – use
Glu and GABA to do that
These are primary neurotransmitters
For many years, these chemicals were not accepted as
Neurotransmitter system criteria:
o They were figured out later that they do fit the criteria
o They are amino acids and derivatives
o Derived from glucose or glutamine change that to glutamate
Storage and release:
o Loaded via vesicular glutamate transporters
Postsynaptic Glutamate receptors:
o 4 different subtypes:
NMDA – ionotropic (i.e. excite the cell)
Kainate – ionotropic
AMPA – ionotropic
mGlu – metabotropic (i.e. inhibit the cell)
Note: mGluRs (of Gi variety) can be presynaptic
Need to get rid of it so it doesn‟t excite the cell constantly, Clearance:
Reuptake via high-affinity glucose transporter (which is called
o can also have EAAT (excitatory amino acid transporter)
type of transporter – picks up more general things GABA:
o Derived from glutamate
Need GAD and B6
Important role of glial
If whole goal is to get more GABA in your system, why don’t you just
drink some GABA?
No – GABA doesn‟t cross the BBB
o BBB can stop things coming in, but also stops things going out
(stops GABA from going out which is good,
Think about synapse because that‟s where all out drug targets are.
What are the alternative approaches?
o post-synaptic receptor activity
o clearance and metabolism
CNS Depressant Mode of Action:
If keep increasing the GABAergic tone (it is dose dependent, if you
have too much in the system you will reach death)
Think of it as a scale:
o surgical anaesthesia …..
A lot of the time we talk about CNS depressants as sedatives, or
sometimes tranquilizers (terminology)
CNS depressants have been used throughout civilization… Bromides first widely used sedative
o half life, take on the half life = these drugs had a very high
toxicity effect (remember graph that goes up and up…that‟s what
Chloral hydrate was the next widely marked sedative
o Used to date-rape people by dropping this into girls drinks
o nowadays, known as "slip someone a Mickey"
o can actually find this still being used typically in rest
homes, in age-related dimensia cases so that people don‟t
get up in the middle of the night etc.
Don‟t remember all Should be able to give ONE example of
this…memorize one of the names
o e.g. Phenobarbital = first used
120 hours half life (take every 5 days) – not that
convenient so making drugs with shorted half lives were
The way they work =
They depress motor cognitive and behavioural functioning
o DOSE-DEPENDANT effects
Can lead to death if a lot is taken – refer to spectrum
there were thousands of deaths from taking these -
not good drugs, safety profile wise...
They facilitate the GABA (A) receptor opening
Site of Action
GABA drugs can work everywhere in your system
they act throughout the CNS
when you start to depress activity in the brainstem, you also
depress your heart rate and your respiratory rate drops off- this
is how it can kill you.
Your reaction time
cognition - learning and memory is impaired
biggest side effect is death Barbituates:
they exhbit a lot of tolerance
o there are 2 types of tolerance:
1. Pharmacodynamics tolerance
2. Pharmacokinetics tolerance
activity of enzymes upregulate, so it increases the
own drugs metabolism (have to keep taking more to
Can exhibit abuse and dependence
Have physiological effects = mostly sleep related = major sleep
o when go off drugs can affect sleep
Also have psychological effects = desire for effect
Small window, therefore quite quickly you start to go into toxicity
Mainstay of sedative prescription up until 1960s, but today not readily
prescribed as anxiolytics due to safety issues.
still around today used for:
o anticonvulsant for epilepsy
o operative sedation/anesthesia
o truth sera?
Is there a drug that can make you tell the truth?
o Some believe truth serums will come back – David Brown,
Washington Post 2006
Why would you take such as drug? Who would use it?
Court of law to maybe get a confession
In a psychiatric sense
Military for interrogation purposes
For sports – get a confession for drug-taking instead of spending
all this money on testing
Are there any truth sera available today?
Potential compounds that have been investigated in the past
o Sodium Amytal? o Scopolamine? – from reading
Is it ethical to administer such a drug to another person?
Maybe if you sign consent to it…it could prove innocence etc?
Could it be used in a malicious way?
Could it be used in a positive way?
Life/death reasons?? – e.g. kidnapped child
Do we have a truth serum today = NO
Clinical records for narcoanalysis found in psychiatry:
1930s – William Bleckwenn demonstrated potential for amytal to
treat catatonic mutism (e.g. stuttering etc)
Today - very contentious amongst medical professionals
There has also been this military drive to use this in prisoners of war
At early stages of CNS depression, many people do become more
talkative does this mean they are telling the truth (filter goes away
when you get drunk, but that doesn‟t imply truth) – need to think
One of the most first prescription drugs to be widely marketed, with
targeted campaigns towar