Once an agonist drug has bound to its receptor, some effector mechanism is activated. The receptor-effector system may be an enzyme in the intracellular space (eg, cyclooxygenase, a target of nonsteroidal anti-inflammatory drugs) or in the membrane or extracellular space (eg, acetylcholinesterase). Neurotransmitter reuptake transporters (eg, the norepinephrine transporter, NET, and the dopamine transporter, DAT, are receptors for many drugs, eg, antidepressants and cocaine. Most antiarrhythmic drugs target voltage-activated ion channels in the membrane for sodium, potassium, or calcium. For the largest group of drug-receptor interactions, the drug is present in the extracellular space, whereas the effector mechanism resides inside the cell and modifies some intracellular process. These classic drug-receptor interactions involve signaling across the membrane. Five major types of transmembrane-signaling mechanisms for receptor-effector systems have been defined (Figure 2–6, Table 2–1).