agonist and antagonist

Partial Agonist:
Substance that bind with receptor but not give maximum effect as full agonist even all receptor are occupied (there is no Emax)

Partial agonist can act as competitive antagonist of full agonist.
competing with the full agonist for receptor occupancy and producing a net decrease in the receptor activation observed with the full agonist alone.
Aripiprazole ( neuroleptic ) act as partial agonist on Dopamine receptor(D).
Dopaminergic pathway is over active this drug will bind with D receptor and act as antagonist so make dopamenergic pathway under active so used in schizophrenia.



inverse agonist is an agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist. A prerequisite for an inverse agonist response is that the receptor must have a constitutive (also known as intrinsic or basal) level activity in the absence of any ligand.
An agonist increases the activity of a receptor above its basal level while an inverse agonist decreases the activity below the basal level. A neutral antagonist has no activity in the absence of an agonist or inverse agonist but can block the activity of either.
The efficacy of a full agonist is by definition 100%, a neutral agonist, 0%, while an inverse agonist has < 0% (i.e., negative) efficacy.
An example of a receptor that possesses basal activity and for which inverse agonists have been identified is the GABAA receptor. Agonists for the GABAA receptor (such as the benzodiazepines alprazolam and diazepam) elicit a sedative effect while inverse agonists have convulsive effects (certain beta-carbolines).


Antagonist:
a drug that does not provoke a biological response itself but blocks or dampens agonist-mediated responses.
antagonists have affinity but no efficacy. or they may interact at unique binding sites not normally involved in the biological regulation of the receptor s activity. Antagonist activity may be reversible or irreversible .
Type of antagonism:
Pharmacological antagonist: Antagonists mediate their effects by binding to the active site ( competitive ) or to allosteric sites ( non competitive ) on receptors, shift agonist curve to the right.

Eg/norepinephrine and prazosin on ? 1 receptor

Physiological ( functional )
The drug bind to site differ from of agonist and give opposite effect of agonist
Eg/ histamine produce bronchospasm ( H1) can be antagonized by epinephrine(?2)
Chemical antagonist:
The drug bind with agonist and produce inert complex
Eg/ protamine with heparine
Kinetic or dispositional antagonism:
Interfer with absorption, distribution, metabolism and excretion of agonist
Eg/ diuretic increase excretion og agonist
Activated charcol decrease absorption (adsorbent)
Alcohol enzyme inducer so decrease metabolism of other drugs
Therapeutic index: measure drug safety
Is ratio of dose that produce toxicity to the dose that produce a clinically desired or beneficial effect in population
TI=TD50/ED50
Large value mean wide range between effective and toxic dose