orthosteric site
The orthosteric site is the receptor's 'main door' — the pocket built to receive the body's own natural messenger. When the endogenous agonist (say, a neurotransmitter or hormone) docks there, it does so at the orthosteric site, and many drugs are designed to bind that same spot.
A drug at the orthosteric site competes directly with the natural ligand: an orthosteric agonist mimics the natural signal, while an orthosteric antagonist blocks the door so the natural ligand cannot get in. This is the textbook site for competitive interactions, the place that defines what 'same binding site' means.
Because the orthosteric site evolved to recognize one shared natural ligand, it is often structurally conserved across closely related receptor subtypes — which makes achieving subtype selectivity there difficult. That conservation is a major reason medicinal chemists also look to allosteric sites, which tend to be less conserved and offer a different route to selective modulation.
Acetylcholine binds the orthosteric site of the muscarinic receptor; atropine is an orthosteric antagonist that occupies that same pocket and blocks acetylcholine from activating it.
The orthosteric site is where the receptor's natural ligand binds.
Orthosteric (the natural ligand's site) contrasts with allosteric (a separate, modulatory site). A drug can act at either; the choice strongly shapes its selectivity and behaviour.