Receptors receive signals
A receptor is a protein that listens. The body sends chemical messages — hormones, neurotransmitters — and receptors are the molecules built to receive them. Most sit in the cell's outer membrane with one part facing the outside world and another reaching inside, so a message arriving outside can be relayed into the cell without the messenger ever crossing the wall. The molecule the receptor naturally listens for is its natural ligand; a drug aimed here either mimics that ligand or jams its slot.
The pocket where the natural ligand normally binds is the orthosteric site — "ortho" meaning the right, proper place. Most receptor drugs aim there because it is the control switch evolution already built. A few clever drugs instead bind elsewhere on the receptor, at an allosteric site, and turn the signal up or down without sitting in the main slot — a theme we return to in guide 5.
GPCRs: the biggest family
The G-protein-coupled receptor (GPCR) family is the superstar of drug targets — a huge group of receptors, each a single chain that threads through the membrane seven times. When a ligand binds the outside, the receptor changes shape, and on the inside it activates a partner called a G protein, which carries the message onward. Because GPCRs sense light, smell, taste, hormones and neurotransmitters, they sit at the controls of an enormous range of biology — which is exactly why a large share of all marketed drugs act on them.
Turn it on or turn it off
Receptor drugs come in two basic flavours. An agonist binds and switches the receptor on, copying the natural signal — useful when the body has too little of a signal. An antagonist binds and blocks the receptor, sitting in the slot like a key that fits but won't turn, so the natural ligand can't get in — useful when there is too much signalling. A classic example is the beta-blocker, an antagonist that calms an over-driven heart by blocking adrenaline's receptor.
Between full-on and full-off lies a gentler option: a partial agonist, which turns the receptor on only partway no matter how much you give. Partial agonists are prized when a full blast would be dangerous but total silence isn't right either — they offer a built-in ceiling on the response. Knowing whether you want on, off, or somewhere in between is the first design choice for any receptor drug.