Let’s take a look at some of the atypical drugs.
There are atypical drugs that will act
through the benzodiazepine receptor,
there are drugs that will act t
hrough the melatonin receptor,
there are also drugs that will act
through the serotonin receptor,
and there are drugs that will act
through the newly discovered orexin receptor.
The atypical drugs that act through the
benzodiazepine receptor include drugs like Zolpidem.
It causes increased flow
through the chloride channel.
Once again, it helps GABA
by inhibiting the ɣ subunit
and it binds between the α and ɣ subunit.
You can see that it’s a slightly different
binding site than both benzodiazepine and flumazenil.
It acts through only one type of receptor
and that receptor which
contains the α1 type of subunit.
More specific actions with this drug,
so you get insomnia control
without some of the other side effects.
Because you’re now acting at
a more specific level of the brain,
this is why this new drugs seem to be
a little bit better for treating insomnia.
Flumazenil or Anexate is an antagonist
to these types of drugs.
And that’s because flumazenil’s
binding point is actually very close
to drugs like Zolpidem’s binding point.
It is used as a reversal agent
in overdoses from these medications.
And as I said before, it binds at a similar
site to both the benzodiazepines and Zolpidem.
Let’s talk about the atypical drugs
that act through the melatonin receptor.
So, Ramelteon is a melatonin agonist.
It is active at the
So it’s very, very useful
in insomnia treatment.
The thing that I like about this class of drugs
is that they have a low risk for abuse.
They are less addictive than the other
medications including benzodiazepines.
Now, one of the downsides is that
it is metabolized to an active metabolite
by cytochrome systems.
So in this regard, it will interact with drugs
like fluvoxamine and the azole antifungals.
So, be aware that you can get
drug interactions with this medication.
Tasimelteion or Heltioz is a very
commonly prescribed medication.
Once again, it also is a melatonin agonist.
Once again, it also works
in the suprachiasmatic nuclei
And it is for the strange disorder called the
non-24 hour sleep-wake disorder in blind people.
So, let me just explain this really quickly,
blind people can’t see
the sun for obvious reasons.
and melatonin is an agent that is naturally made
in the brain in response to light.
So it helps us with our sleep-wake cycles.
Blind people don’t have that cues so they
sometimes have altered melatonin levels.
This drug is used to help blind people
sleep at night and wake during the day.
It is the only drug I believe that is currently
licensed for use in this particular disorder.
And that’s why I do want you to remember
this particular melatonin antagonist
because it’s probably the only one that will see
a long time indicated for the sleep disorder.
Let’s move one to the atypical drugs that act
through the newly discovered orexin receptor.
Suvorexant is an orexin receptor antagonist.
It does have very good hypnotic profiles.
Let’s take a look at its profile issues
now with respect to safety.
The safety in addictive risk persons is unknown.
So we don’t know if it’s going to be
a highly addictive medication or not.
The safety in pregnancy is currently unknown
and the safety in breastfeeding
is currently unknown.
So we don’t know a lot of things
about this new class of drugs;
as time goes on we’ll know more and more.
Now, you should be aware that
this drug class does interact currently
with all cytochrome system drugs.
So it’s an important consideration when
you have people on multiple medications
as to whether or not you’re going
to use these medications.
Atypical drugs that act through the serotonin
receptor include Buspirone or BuSpar.
This is a very, very commonly used medication.
It is a selective anxiolytic;
it has minimal sedative effects
and motor effects or rebound.
It acts on the 1A serotonin receptor.
Now, serotonin receptors are
sometimes called serotonin receptors,
sometimes they are called 5HT receptors.
So just to be clear,
5HT and serotonin are the same thing.
This drug has a very slow onset of action.
And it’s used in generalized anxiety disorders
but not in panic disorders.
Generalized anxiety disorders
require a long-term treatment;
panic disorders are relatively rapid
on rapid off kinds of problems
so long-term drugs don’t work as well
in these types of situations.
We’re going to see the psychiatry lectures
later on for more information.
So I won’t talk about it too much today.
Side effects with these medications,
the thing I want you
to remember is once again,
these drugs do have interactions
through the cytochrome system.
They can cause tachycardia,
they can cause miosis
and GI distress as well.
The thing that you want
to remember about this drug
and the thing that is important for your
exam as well as in practice is that
this is one of the few drugs
that’s actually safe in pregnancy.
So this is where it comes into play.
So let’s summarize some of the sleep disorder
drugs that we use in modern medicine.
We used to use a lot of benzodiazepines
but not so much now because they’ve
been replaced by these newer drugs.
They start with the letter Z.
So sometimes it’s easy to remember them;
they all have Z or zed
in their nomenclature.
So it’s sometimes easier for us
to pick them out.
They have α-specific atypical agents
acting through the benzodiazepine receptor
and these are very effective agents
in sleep and insomnia as well;
and the newer melatonin–specific agents
are rapidly increasing in popularity.
There is also a product out in the
herbal product world called Melatonin.
A lot of people like to by melatonin
over the counter as a herbal product.
Unfortunately, we don’t really know
what’s in these bottles.
Some of the bottles that are
being sold in herbal product stores
have no melatonin specific agents.
And some of them have too much.
So it’s very hard to predict whether
or not these agents are useful or not.
There is biological plausibility for them
but I say buy or beware and you’re
better off just getting something
that actually has a US pin number.
There’s going to be a specific subset
of patients who are unique
and these are people who rely
heavily on motor skills.
So I want you to think of the plastic surgeons
and neurosurgeons in your world
and think about if they have anxiety.
What are we going to treat them with?
Well, buspirone or BuSpar
has little psychomotor side effects.
So, if you have a person who is
heavily dependent on motor skills;
whether they are an artist or a surgeon,
this is a great choice.
The other reason why this is a good choice
is because it’s safe in pregnancy.
A nice thing about these drugs,
this particular class of drug is that
it has a low risk of addiction.