Chapter 1: General Pharmacological Principles

Back to chapter

1.7:

Drug-Receptor Bonds

JoVE Core
Pharmacology

Bu içeriği görüntülemek için JoVE aboneliği gereklidir. Oturum açın veya ücretsiz deneme sürümünü başlatın.

JoVE Core Pharmacology

Drug-Receptor Bonds

Önceki Video
1.2: Preclinical Development: Overview

Sonraki Video
1.8: Drug-Receptor Interactions

Diller

Paylaş

English العربية 中文 Nederlands français Deutsch עברית italiano 日本語 한국어 português русский español Türkçe

Drugs bind their targets or receptors using chemical forces, such as covalent bonds, electrostatic interactions, and hydrophobic effects. Covalent bonds are strong and irreversible and rarely occur except in toxic situations. DNA-alkylating anticancer agents form covalent bonds with cancer cells' DNA and arrest their cell division. However, such agents are nonselective and modify the surrounding healthy cells' DNA. In contrast, non-covalent interactions are weaker but more selective because a drug must precisely fit its target to form such bonds. Most drugs and receptors interact via electrostatic interactions. Electrostatic interactions are strong between oppositely charged ionized molecules and weak in the case of hydrogen bonds and van der Waals forces. Another type of weak interaction occurs due to the hydrophobic effect when drugs interact with the internal hydrophobic pockets of receptors and exclude surrounding water molecules. Such selective interactions of drugs with their receptors modify the activity of target cells without affecting other cells.

1.7:

Drug-Receptor Bonds

Drug-receptor bonds are formed through various chemical forces when drugs interact with target cells. Covalent bonds, strong and irreversible, are exemplified by DNA-alkylating anticancer agents that inhibit cell division. However, such irreversible drug binding lacks selectivity and can modify the DNA of the surrounding healthy cells. Covalent binding often contributes to tissue toxicity, as seen with chloroform and paracetamol metabolites binding to the liver, causing hepatotoxicity.

In contrast, noncovalent interactions are weaker but more selective, requiring a precise fit between the drug and its target. Most drug-receptor interactions occur through electrostatic interactions, ranging from strong ionic linkages to weaker hydrogen bonds and van der Waals forces. The hydrophobic effect occurs when lipophilic drugs interact with hydrophobic pockets within receptors, excluding surrounding water molecules.

The selectivity of drug-receptor interactions must allow drugs to modify the activity of target cells without affecting others. Covalent bonds are highly reactive but lack selectivity, while weaker bonds provide greater selectivity due to the requirement for an exact fit. Designing highly selective drugs involves avoiding highly reactive molecules that form covalent bonds and instead opting for weaker bond formation.

Etiketler

Drug-receptor Bonds Covalent Bonds Noncovalent Interactions Selectivity Electrostatic Interactions Ionic Linkages Hydrogen Bonds Van Der Waals Forces Hydrophobic Effect Lipophilic Drugs Selectivity Of Drug-receptor Interactions Reactive Molecules