Mechanism of action of cocaine is:

Cocaine is a potent central nervous system stimulant and local anesthetic. Its primary indirect sympathomimetic mechanism of action is blocking catecholamine uptake by the presynaptic axonal terminal. Specifically, cocaine competitively binds to and inhibits the monoamine transporters, primarily the dopamine transporter (DAT) and norepinephrine transporter (NET). By preventing the reuptake of dopamine and norepinephrine back into the presynaptic neuron, cocaine prolongs and intensifies catecholamine action at synaptic receptors. This inhibition leads to accumulation of catecholamines in the synaptic cleft, producing intense euphoria, peripheral vasoconstriction, hypertension, and tachycardia. Additionally, cocaine blocks voltage-gated sodium channels, providing local anesthetic properties.

A: Inhibiting the Na-Cl cotransporter is the mechanism of action of thiazide diuretics acting in the distal convoluted tubule of the nephron.

B: Muscarinic agonists stimulate parasympathetic acetylcholine receptors; cocaine acts as a sympathomimetic agent by increasing synaptic catecholamine levels.

C: Beta-2 receptor agonists like albuterol selectively activate bronchial smooth muscle receptors, whereas cocaine indirect sympathomimetic effects stem from uptake inhibition.

D: Beta-1 receptor antagonists (beta-blockers) decrease heart rate and contractility, contrasting directly with cocaine's indirect stimulation of beta-1 adrenergic receptors.

1. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 14th Ed., Chapter 10: Adrenergic Agonists and Antagonists, pp. 191–210.

2. Rang & Dale's Pharmacology, 9th Ed., Chapter 49: Local Anaesthetics and Allied Drugs, Elsevier, pp. 602–607.

3. MIT OpenCourseWare: Brain and Cognitive Sciences – Neuropharmacology of Drugs of Abuse.