oMixed agonist-antagonist – evidenced when a drug acts as an agonist by itself , but blocks the
activity of another agonist in the same system.
-Cooper et al – view of the receptor as having one elemental “binding” site and another elemental “effector”
-Receptors exist in an active and an inactive configuration, each of which is capable of combining with a drug
molecule. Therefore, the ratio of the drugs affinity for the two configurations determines whether the drug
will be an agonist or antagonist.
-Agonist with high efficacy causes maximal response by activating proportionally fewer receptors, whereas
with low efficacy, the agonist may fail to elicit a maximal response compared with compounds with higher
-Antagonists – drugs that exert their effects by blocking the action of agonists.
o Competitive antagonists – ligands that bind to these sites but do not change the complex
oPhysiological antagonism – form of drug interaction in which two drugs act at two different kinds
of receptors – that is receptors whose biological actions oppose each other.
-Ionotropic receptors – produce very rapid changes in neuronal activity
oComprised of 5 subunits (greek symbols alpha beta theta, tri) comprised of a string of amino acids.
The subunits form an internal pore of ion channel through which specific types of ions can flow
through to alter the excitability of the neuron.
oVarious binding sites, x, y, z. for ligands on subunits – which when occupied may change the
conformation of the receptor to increase (or decrease) the passage of ions through the channel.
oAllosteric modulators - May possess binding sites for ligands that DO NOT directly alter ion flow,
but which modulate the influence of agonists binding to other sites on the complex. Ex –
benzodiazepines, like Valium, used for sedation and reduction of anxiety related symptoms is a
indirect agonist and works like this.
-Metabotropic Receptors - Produce relatively slow-developing and long-lasting effects on neurons.
oComprised of a long string of amino acids that's loops back and forth through the neuronal
oCoupled with a G-Protein, specialized and embedded in the inside membrane, which is in turn
connected to a effector unit.
o1 type of receptor - G-protein is linked to an ion channel. Therefore when the receptor is activated
a subunit of the g-protein breaks off and binds with the ion channel and opens it.
oSecondary Messengers - Effector is an anzyme that is activated when a subunit of the g-protein
breaks off and bind to the enzyme. This enzyme then triggers the forumation of a bunch of
molecules inside the neurons axon which eventually lead to biochemical alterations within the
-Key- and-lock analogy –
-Sedvall &Farde – 1990s – identified approximately 300 receptor types.
Parmacogenetics – attempt to discover differential effects of a drug in different patients, depending on the presence of
inherited variated in genes, with the goal of providing more patient-disease-specific health care.
Pharmacogenomics – attempt to discover differential effects of compounds, either in vivo or in vitro, on gene
expression among all genes that are expressed in humans, with the goal of finding the “best” drug candidate from a
given series of compounds under evaluation.
The usual way of discussing a drug’s effects in terms of dose-response function – expresses the relationship between
the dose administered and the response observed.
-Determined by taking groups of individuals, administering each group a different amount of the drug in
question, and then waiting for sufficient time as to assess the degree of effect or the number of individuals
displaying a specified effect of the drug.
-Placebo – one group is administered a substance without any physiological effects instead of the drug itself.
oSaline – is most often used in animals – because it is a combination of water and sodium chloride
that is normally found within the human body. Therefore no change occurs based on drug.