Medicinal Chemistry I

Structure-Activity Relationship mimic catecholamines (epinephrine, norepinephrine, dopamine) by stimulating adrenergic receptors (α and β). Their activity depends on structural modifications affecting receptor selectivity, metabolism, and CNS penetration. Key Structure-Activity Relationship Features Catechol Ring Substitutions 3,4-Dihydroxy (Catechol): High α/β activity, rapid metabolism (e.g., Epinephrine, Norepinephrine). Single Hydroxyl (-OH) Group: Reduces metabolism, increases α1 selectivity (e.g., Phenylephrine). No … Read more

Sympathomimetic Agents the actions of endogenous catecholamines. They are broadly classified into three groups based on their mechanism of action: Classification of Sympathomimetic Agents Sympathomimetic agents are drugs that mimic the actions of the sympathetic (adrenergic) nervous system. They are classified based on their mechanism of action in activating adrenergic receptors. 1. Direct-Acting Sympathomimetics Mechanism: These … Read more

Adrenergic receptors are G-protein-coupled receptors (GPCRs) that mediate the effects of norepinephrine and epinephrine. Adrenergic receptors are classified into Alpha (α) and Beta (β) receptors, with further subtypes. Alpha-Adrenergic Receptors (α-Receptors) These receptors mainly mediate vasoconstriction and smooth muscle contraction. α1-Receptors (Gq-coupled) Mechanism: Activate phospholipase C (PLC) → Increase IP3 & DAG → Increase intracellular … Read more

Catecholamines are degraded primarily by Monoamine Oxidase (MAO) and Catechol-O-Methyltransferase (COMT) into inactive metabolites, which are excreted in urine. Steps of Catecholamines Catabolism MAO Pathway: MAO (located in neuronal mitochondria) oxidizes catecholamines into dihydroxyphenylglycol aldehyde. This is further converted into vanillylmandelic acid (VMA) for excretion. COMT Pathway: COMT methylates catecholamines to form metanephrine and normetanephrine. … Read more

Catecholamines Biosynthesis (dopamine, norepinephrine, and epinephrine) are synthesized from tyrosine in adrenergic neurons and the adrenal medulla. Steps of Catecholamines Biosynthesis Tyrosine Transport & Hydroxylation: Tyrosine, derived from diet or synthesized from phenylalanine, is transported into neurons. Tyrosine hydroxylase (TH) converts tyrosine into L-DOPA (Rate-limiting step). Decarboxylation to Dopamine: DOPA decarboxylase converts L-DOPA into dopamine. … Read more

Sympathetic Nervous System (SNS) Definition  The Sympathetic Nervous System (SNS) is a division of the autonomic nervous system responsible for the “fight or flight” response. Drugs acting on the SNS either stimulate (sympathomimetics) or inhibit (sympatholytic) its activity by targeting adrenergic receptors (α and β), affecting heart rate, blood pressure, bronchodilation, and metabolic processes. Adrenergic … Read more

Parasympathetic Nervous System (PNS) Definition  The Parasympathetic Nervous System (PNS) are drugs that mimic or enhance the effects. They promote “rest and digest” functions by stimulating muscarinic and nicotinic receptors, leading to effects such as reduced heart rate, increased glandular secretions, and enhanced digestive activity. Cholinergic Agonists (Parasympathomimetics) Mimic acetylcholine, stimulating the PNS. Effects: ↓ … Read more

Neurons and Synapses Definition  neurons and synapses, representing the fundamental unit of neural communication where electrical or chemical signals are transmitted from one neuron to another. It emphasizes the inseparable relationship between the nerve cell (neuron) and its connection point (synapse) in processing and transmitting information within the nervous system. Neurons Neurons are the fundamental … Read more

The nervous system is a complex network of nerves and cells, known as neurons, that transmit signals between different parts of the body. It essentially functions as the body’s electrical wiring. It is divided into two main components: Central (CNS) Peripheral (PNS) This system is fundamental to everything the body does, from sensing heat and … Read more

Factors Affecting Drug Metabolism: It is influenced by biological, chemical, and stereochemical factors, affecting drug efficacy, clearance, and potential toxicity. Biological and Chemical Factors Affecting Drug Metabolism Genetic Polymorphisms Enzyme Variability: Differences in genes encoding drug-metabolizing enzymes (e.g., CYP450) lead to variations in metabolic rates. Metabolizer Phenotypes: Individuals can be poor, intermediate, extensive, or ultra-rapid … Read more