question: what actually happens when a molecule activates a receptor vs when an inhibitor molecule just blocks it?
comment: Think of the molecule as a key and the receptor as a lock. The "real" key will always be able to open the lock as intended. However, there are some keys that coincidentally have a similar shape to the "real" key, but not similar enough to open the lock. So when you try to open the lock with the similar key, instead of opening the lock, it gets jammed and it gets stuck. The lock is still locked while the key is stuck, which is a metaphor for how the inhibitor just gets stuck in the receptor without causing a biological effect.
passages: Most of the ARBs have the same pharmacophore so the difference in their biochemical and physiological effects is mostly due to different substituents. Activity of a drug is dependent of its affinity for the substrate site and the length of time it binds to the site.
   It is this phenomenon that gives rise to drug specificity. Of course, drugs do not only act on receptors: they also act on ion channels, enzymes, and cell transporter proteins. these hydrogen bonds are so powerful than the ionic bonds.
  
  Section::::How shape of drug molecules affect drug action.
  
  When talking about the shape of molecules, biochemists are mainly concerned with the three-dimensional conformation of drug molecules. There are many isomers of a particular drug, and each one will have its own effects. Differences in isomer affect not only what the drug activates, but also changes the potency of each drug.
   BULLET::::- A conformational change in the target is induced by the stimulus which results in a change in target function. This change in function can mimic the effect of the endogenous substance in which case the effect is referred to as receptor agonism (or channel or enzyme activation) or be the opposite of the endogenous substance which in the case of receptors is referred to as inverse agonism.
  
  Section::::Drug targets.
   Once the receptors are activated, they either trigger a particular response directly on the body, or they trigger the release of hormones and/or other endogenous drugs in the body to stimulate a particular response.
  
  Section::::Short note on receptors.
  
  Drugs interact with receptors by bonding at specific binding sites. Most receptors are made up of proteins, and the drugs can therefore interact with the amino acids to change the conformation of the receptor proteins.
  
  These interactions are very basic, just like that of other chemical bondings:
  
  Section::::Short note on receptors.:Ionic bonds.
   Uncompetitive antagonist
  
  Uncompetitive antagonists differ from non-competitive antagonists in that they require receptor activation by an agonist before they can bind to a separate allosteric binding site. This type of antagonism produces a kinetic profile in which "the same amount of antagonist blocks higher concentrations of agonist better than lower concentrations of agonist". Memantine, used in the treatment of Alzheimer's disease, is an uncompetitive antagonist of the NMDA receptor.
   Section::::How shape of drug molecules affect drug action.:Potency.
  
  Potency is a measure of how much a drug is required in order to produce a particular effect. Therefore, only a small dosage of a high potency drug is required to induce a large response. The other terms used to measure the ability of a drug to trigger a response are:
  
  BULLET::::- Intrinsic Activity which defines:
  
  BULLET::::- Agonists as having Intrinsic Activity = 1
  
  BULLET::::- Antagonists as having Intrinsic Activity = 0
  
  BULLET::::- and, Partial Agonist as having Intrinsic Activity between 0 and 1
   Section::::Inhibitory receptors.
  
  There are two types of inhibitory receptors:
  
  Section::::Inhibitory receptors.:Ionotropic receptors.
   BULLET::::- "Antagonists" bind to receptors but do not activate them. This results in a receptor blockade, inhibiting the binding of agonists and inverse agonists. Receptor antagonists can be competitive (or reversible), and compete with the agonist for the receptor, or they can be irreversible antagonists that form covalent bonds (or extremely high affinity non-covalent bonds) with the receptor and completely block it. The proton pump inhibitor omeprazole is an example of an irreversible antagonist. The effects of irreversible antagonism can only be reversed by synthesis of new receptors.
   BULLET::::2. Uncompetitive antagonists, when the antagonist binds to the receptor irreversibly and is not released until the receptor is saturated. In principle the quantity of antagonist and agonist that binds to the receptor will depend on their concentrations. However, the presence of the antagonist will cause the main drug to be released from the receptor regardless of the main drug's concentration, therefore all the receptors will eventually become occupied by the antagonist.
  
  BULLET::::2. Heterodynamic competitors, if they act on distinct receptors.
   BULLET::::3. Antagonists, if they bind directly to the receptor's main locus but their effect is opposite to that of the main drug. These include:
  
  BULLET::::1. Competitive antagonists, if they compete with the main drug to bind with the receptor. The amount of antagonist or main drug that binds with the receptor will depend on the concentrations of each one in the plasma.
   Activity is generally dosage-dependent. Further, it is common to have effects ranging from beneficial to adverse
  
  for one substance when going from low to high doses. Activity depends critically on fulfillment of the ADME criteria. To be an effective drug, a compound not only must be active against a target, but also possess the appropriate ADME (Absorption, Distribution, Metabolism, and Excretion) properties necessary to make it suitable for use as a drug.
   The graph shown represents the conc-response for two hypothetical receptor agonists, plotted in a semi-log fashion. The curve toward the left represents a higher potency (potency arrow does not indicate direction of increase) since lower concentrations are needed for a given response. The effect increases as a function of concentration.
  
  Section::::Multicellular pharmacodynamics.
   Uncompetitive antagonists differ from non-competitive antagonists in that they require receptor activation by an agonist before they can bind to a separate allosteric binding site. This type of antagonism produces a kinetic profile in which "the same amount of antagonist blocks higher concentrations of agonist better than lower concentrations of agonist". Memantine, used in the treatment of Alzheimer's disease, is an uncompetitive antagonist of the NMDA receptor.
  
  Section::::Types.:Silent antagonists.
   Many antagonists are reversible antagonists that, like most agonists, will bind and unbind a receptor at rates determined by receptor-ligand kinetics.
   Section::::Pharmacodynamics.:Affinity.
   Our understanding of the mechanism of drug-induced receptor activation and receptor theory and the biochemical definition of a receptor antagonist continues to evolve. The two-state model of receptor activation has given way to multistate models with intermediate conformational states. The discovery of functional selectivity and that ligand-specific receptor conformations occur and can affect interaction of receptors with different second messenger systems may mean that drugs can be designed to activate some of the downstream functions of a receptor but not others. This means efficacy may actually depend on where that receptor is expressed, altering the view that efficacy at a receptor is receptor-independent property of a drug.
   BULLET::::- irreversible covalent – The stimulus is permanently bound to the target through irreversible chemical bond formation.
  
  Depending on the nature of the stimulus, the following can occur:
  
  BULLET::::- There is no direct change in the biological target, but the binding of the substance prevents other endogenous substances (such as activating hormones) from binding to the target. Depending on the nature of the target, this effect is referred as receptor antagonism, enzyme inhibition, or ion channel blockade.
   Section::::Common mechanisms of second messenger systems.
  
  There are several different secondary messenger systems (cAMP system, phosphoinositol system, and arachidonic acid system), but they all are quite similar in overall mechanism, although the substances involved and overall effects can vary.
  
  In most cases, a ligand binds to a membrane-spanning receptor protein molecule. The binding of a ligand to the receptor causes a conformation change in the receptor. This conformation change can affect the activity of the receptor and result in the production of active second messengers.
   Section::::History.:Nature of receptor–drug interactions.:Receptor occupancy model.:Competitive inhibition models.
   Binding affinity data alone does not determine the overall potency of a drug. Potency is a result of the complex interplay of both the binding affinity and the ligand efficacy. Ligand efficacy refers to the ability of the ligand to produce a biological response upon binding to the target receptor and the quantitative magnitude of this response. This response may be as an agonist, antagonist, or inverse agonist, depending on the physiological response produced.
  
  Section::::Selective and non-selective.
   Many drug molecules are enzyme inhibitors, so their discovery and improvement is an active area of research in biochemistry and pharmacology. A medicinal enzyme inhibitor is often judged by its specificity (its lack of binding to other proteins) and its potency (its dissociation constant, which indicates the concentration needed to inhibit the enzyme). A high specificity and potency ensure that a drug will have few side effects and thus low toxicity.
   Affinity is a measure of the tendency of a ligand to bind to its receptor. Efficacy is the measure of the bound ligand to activate its receptor.
  
  Section::::Binding and activation.:Agonists versus antagonists.
  
  Not every ligand that binds to a receptor also activates that receptor. The following classes of ligands exist:
  
  BULLET::::- "(Full) agonists" are able to activate the receptor and result in a strong biological response. The natural endogenous ligand with the greatest efficacy for a given receptor is by definition a full agonist (100% efficacy).
   Section::::Structure-based drug design.
   BULLET::::- Orthosteric agonists and antagonists: bind to the main receptor site (the site where GABA normally binds, also referred to as the "active" or "orthosteric" site). Agonists activate the receptor, resulting in increased Cl conductance. Antagonists, though they have no effect on their own, compete with GABA for binding and thereby inhibit its action, resulting in decreased Cl conductance.
   Section::::Types.
  
  Section::::Types.:Competitive.
  