Eg. Aripiprazole prevents dopamine from binding to its receptors and eliminates the
excessive stimulation, this is a antipsychotic drugs to treat Schizophrenia.
-Drugs may produce complex patterns of response, which has led to the terms inverse
agonist and mixed agonist-antagonists eg. Opiates and benzodiazepines
-An inverse agonist is defined as a drug that appears to act through the same receptor as
an agonist but produces effects opposite to those of the agonists; thus, it can also be
viewed as a type of agonist.
-A mixed agonist-antagonists is evidenced when a drug acts as an agonist by itself, but
blocks the activity of another agonist in the same system.
-Functionally, mixed agonist-antagonists and partial agonists have similar properties; that
is, by themselves they exert agonist effects but are capable of reducing the effects of full
agonists in the same system.
-The basic difference appears to be that a partial agonist works on the same receptors as
full agonist, but because of its lower maximal effect and its ability to reduce the full
agonist’s access to those receptors, the maximal effect of the full agonists is reduced if
the two are given together.
-In contrast, a mixed agonist-antagonist may be a full agonist at one type of receptor and
a complete antagonist at another type of receptor: thus when combined with a full agonist
that activated both types of receptors, the mixed agonist-antagonist blocks some of the
effects that would normally occur with the full agonist alone.
-One view of the receptor is that it consists of one element comprising a “binding” site
and another element comprising an “effector” site.
-This model very easily handles cases in which a drug with a molecular structure
compatible with both sites is an agonist from binding and thus prevents its actions: that is,
the later drug acts as an antagonist.
-However, this model has difficulties in explaining some phenomena, most notably
inverse agonism and mixed agnonism-antagonism.
-Another model proposes that receptors exist in an active and in inactive configuration,
each of which is capable of combining with a drug molecule.
-Whether a drug acts as an antagonist or agonist will be determined b the ratio of the
drug’s affinity for the two configuration.
Eg. A drug may combine with the inactive configuration, preventing the receptor from
attaining its active configuration, so that the drug acts as an antagonist.
-These and other models of receptors are subject to changes as we find more information
-There are two classes of receptors
-The first class of receptors, which produce very rapid changes in neuronal activity, are
called ionotropic receptors
-Most are composed of five subunits made up of- ( , , , ) which are comprised of
strings of amino acids.
-These subunits form an internal pore or channel through which specific types of ions
(electrically charged ion eg. Na, K+ etc.) can flow to alter the excitability of the neuron.