Drug Receptor Interaction

Pharmaceutical industry and drug development - 34/100 drugs on the market target GPCR Physiology of endogenous transmitters - Act primarily upon receptor targets Chemical toxicity - Many toxic mechanisms are receptor mediated Viral toxicity - Viruses and other microorganisms can target receptors

Agonist that does not produce as strong a response as the full agonist. Has antagonistic properties

An agonist that produces an opposing biological response to that observed by a full agonist

Ability of a drug to elicit a biological response from a drug receptor interaction The more effect the drug has, the more efficacious

Hydrogen bonding - Reversible binding dissociation Ionic VdW forces Covalent binding - Irreversible, poor dissociation

Morphine - Opioid receptors, brain painkiller

Law of mass action - Dependent on concentration of the reactants involved Agonist + Receptor -> <- Agonist-Receptor complex AR Association rate k1 Dissociation rate k-1

More receptors bind to drug drug-receptor interaction. Graph begins to level out as more and more receptors are occupied, graph plateaus. Saturation

Measure of affinity - Concentration of drug where 50% of max number of receptors are bound by the drug The ability of a drug molecule to bind to a receptor site

max number of receptors bound by the drug

The concentration of the drug needed for the effect. The less concentration required, the more potent the drug

E.g. buprenorphine for opioid addiction Present at receptors - High affinity, but less efficacy Reduces withdrawal effects Reduces additive ‘highs’ Heroin-induced highs are reduced in presence of partial agonist

Agonist and antagonist compete for same binding site. [A] must increase to overcome antagonist binding to receptors.

Antagonist binds to a different site from the agonist e.g. Ketamine blocks glutamine receptors by acting at a different site in the receptor structure to glutamate