Identify two distinct pharmacological agents, approved for tobacco cessation, that do not involve nicotine replacement.

Varenicline is a pharmacological agent approved for tobacco cessation, meaning it is a medicine used to help people stop using tobacco. It does not involve nicotine replacement, which is a method of providing nicotine to the body to ease withdrawal. Instead, varenicline works by acting as a partial agonist at specific nicotinic acetylcholine receptors in the brain, primarily the alpha4beta2 subtype. Receptors are protein molecules on the surface of cells that bind to specific substances to produce an effect. A partial agonist is a substance that binds to and activates a receptor but produces only a partial response compared to a full activator like nicotine. By partially stimulating these receptors, varenicline helps to reduce the severity of nicotine withdrawal symptoms, which are unpleasant physical and mental effects experienced when stopping nicotine, and cravings, which are intense desires for nicotine. Additionally, because varenicline binds strongly to these receptors, it blocks nicotine from tobacco smoke from binding, thereby decreasing the pleasurable and rewarding effects of smoking. This dual action helps individuals quit by making smoking less rewarding and withdrawal less severe, without providing nicotine itself. Bupropion sustained-release, often referred to as bupropion SR, is another distinct pharmacological agent approved for tobacco cessation that does not involve nicotine replacement. Its precise action for tobacco cessation is not fully understood, but it is believed to primarily work by inhibiting the reuptake of two key neurotransmitters in the brain: norepinephrine and dopamine. Neurotransmitters are chemical messengers that transmit signals between nerve cells. Reuptake inhibition means that bupropion blocks the reabsorption of these neurotransmitters back into the nerve cells that released them, leading to higher levels of norepinephrine and dopamine in the spaces between nerve cells. Increased levels of these neurotransmitters are thought to help alleviate nicotine withdrawal symptoms and reduce cravings by affecting brain pathways involved in reward and addiction. Unlike nicotine replacement therapies, bupropion SR directly modulates these brain chemicals rather than supplying nicotine to the body.