Making and unmaking norepinephrine
Norepinephrine is a catecholamine, built step by step from the amino acid tyrosine. Unlike acetylcholine, it is not mainly destroyed by an enzyme in the synapse. Instead, after it delivers its message, most of it is sucked back up into the nerve ending by a transporter and reused — a process called reuptake. This recycling step is itself a famous drug target: block the transporter and you raise norepinephrine in the synapse, the basis of several stimulant and antidepressant actions.
The adrenoceptor family
Adrenoceptors are all GPCRs, but they split into alpha-adrenoceptors and beta-adrenoceptors — another decisive receptor subtype story. Each couples to a different second messenger system, so each does something different even when stimulated by the same norepinephrine. The trick to all sympathomimetic pharmacology is simply learning where each subtype lives.
alpha-1 : blood vessels (smooth muscle) -> vasoCONSTRICTION, BP up alpha-2 : nerve endings (presynaptic) -> dampens further NE release (brake) beta-1 : heart -> rate up, force up beta-2 : airways, some vessels, uterus -> bronchoDILATION, relaxation beta-3 : fat tissue, bladder -> lipolysis, bladder relaxation
Reading the table at the bedside
This one table predicts an enormous amount. A drug that hits beta-1 speeds and strengthens the heart — useful in shock, dangerous in a fast arrhythmia. A drug that hits beta-2 opens airways — the basis of asthma relievers, with a tremor as a giveaway side effect. A drug that hits alpha-1 tightens vessels and raises blood pressure, and the same logic explains why an alpha blocker drops it. The alpha-2 receptor is the odd one out: it sits *before* the synapse and acts as a brake, so an agonist there actually quietens the sympathetic system — the mechanism of some antihypertensives.