Unit-II_Medichem_1_Adrnergic System

Adrenergic agents are drugs that stimulate the adrenergic receptors, mimicking the effects of adrenaline and noradrenaline.

A receptor transduction mechanism is a process by which a receptor converts an external signal into a cellular response, often involving a series of biochemical events.

CaMKs stands for Ca2+/calmodulin-dependent protein kinases, which are a family of enzymes that are activated by the binding of calcium ions and calmodulin.

Salbutamol is a moderately selective beta(2)-receptor agonist used as a bronchodilator to manage asthma and other chronic obstructive airway diseases.

Clonidine is a medication that treats high blood pressure by stimulating α2A receptors in the brain stem, which decreases peripheral vascular resistance and lowers blood pressure. It is also used for attention deficit hyperactivity disorder, anxiety disorders, withdrawal from substances, migraine, menopausal flushing, diarrhea, and certain pain conditions.

Adrenomimetic agents are substances that mimic the action of adrenaline, activating adrenergic receptors.

The R-isomer, levalbuterol, is responsible for bronchodilation.

Dobutamine is a direct-acting agent primarily used to treat acute but potentially reversible heart failure by stimulating β1-adrenoceptors of the heart, which increases contractility and cardiac output.

Phentolamine is a synthetic imidazoline with alpha-adrenergic antagonist activity that binds to alpha-1 and alpha-2 receptors, resulting in a decrease in peripheral vascular resistance and vasodilatation.

Adrenolytic agents are drugs that block the effects of adrenaline and noradrenaline by inhibiting adrenergic receptors.

Propylhexedrine is a monoamine releasing stimulant that acts as a norepinephrine and dopamine releaser in the central nervous system, binding to and activating alpha-adrenergic receptors in the respiratory tract, leading to vasoconstriction and relief of nasal congestion.

The S-isomer increases bronchial reactivity.

Phenoxybenzamine non-selectively and irreversibly blocks the postsynaptic alpha-adrenergic receptor in smooth muscle, preventing vasoconstriction, relieving vasospasms, and decreasing peripheral resistance and blood pressure.

(6a R ,9 R )- N -[(2 S )-1-Hydroxybutan-2-yl]-4,7-dimethyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide, a drug that inhibits or blocks the effects of serotonin.

Phenylephrine is a postsynaptic α 1 -receptor agonist that causes vasoconstriction, increases systolic and diastolic pressures, and has little effect on β-receptors of the heart.

Mixed adrenergic agonists are compounds that activate adrenergic receptors through both direct binding and the release of endogenously-stored norepinephrine from presynaptic terminals.

Ligand-Gated Ion Channels are a type of receptor transduction mechanism that opens or closes in response to the binding of a ligand, allowing ions to flow across the membrane. Examples include Nicotinic acetylcholine receptors, GABA receptors, and 5-HT3 receptors.

Serotonin is described as a central neurohumoral agent involved in vascular headaches, acting to lower pain threshold and influencing gastrointestinal motility and connective tissue repair.

Phenylephrine is used as a nasal decongestant, mydriatic, and to prolong local anesthetic action.

Ephedrine is a mixed-acting adrenergic agonist that increases the activity of noradrenaline on adrenergic receptors and is derived from plants in the genus Ephedra.

Labetalol is a selective alpha-1 and non-selective beta adrenergic blocker used to treat high blood pressure by blocking adrenergic receptors, which slows sinus heart rate, decreases peripheral vascular resistance, and decreases cardiac output.

Prazosin is a synthetic piperazine derivative and an alpha-1 adrenergic receptor inhibitor used primarily as an anti-hypertensive, resulting in decreased total systemic vascular resistance without rebound or reflex tachycardia.

G-Protein Coupled Receptors (GPCRs) are a class of receptors that activate intracellular signaling pathways through the binding of a ligand, which causes a conformational change in the receptor. Examples include Cholinergic Muscarinic receptors, Histaminic receptors, and Adrenergic receptors.

The biochemical process by which catecholamines, such as dopamine, norepinephrine, and epinephrine, are produced from the amino acid tyrosine.

Phenylephrine causes an increase in systolic and diastolic pressures and can lead to reflex bradycardia.

Carvedilol is a nonselective beta-adrenergic blocking agent with alpha1-blocking activity, indicated for the treatment of hypertension and mild or moderate heart failure, acting through nonselective β-adrenoreceptor blocking in the S(-) enantiomer and α-adrenergic blocking in both R(+) and S(-) enantiomers.

Dihydroergotamine is indicated for the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes.

Nuclear receptors, also known as steroid or thyroid receptors, mediate regulation of DNA transcription and induce synthesis of specific proteins, primarily located inside the nucleus and responsive to lipophilic ligands.

Kinase-Linked Receptors are receptors that, upon ligand binding, activate intracellular kinase activity, leading to phosphorylation of proteins and subsequent cellular responses. Examples include Insulin receptors, Growth factor receptors, and Cytokine receptors.

The process by which catecholamines are secreted from nerve terminals or adrenal medulla into the bloodstream in response to stimuli.

Dopamine is a natural catecholamine and a precursor to norepinephrine in noradrenergic nerves, producing positive chronotropic and inotropic effects on the myocardium.

Bitolterol is an adrenergic bronchodilator prodrug that widens constricted airways in the lungs by relaxing the smooth muscles surrounding the bronchial passages.

Phenylephrine is chemically described as 3-[1-hydroxy-2-(methylamino)ethyl]phenol.

Drugs that bind to but do not activate alpha-adrenergic receptors, thereby blocking the actions of endogenous or exogenous adrenergic agonists.

Kinase-linked receptors, also known as Tyrosine kinase receptors, are receptors for various hormones and growth factors that contain tyrosine kinase in their intracellular domain, differing from ion-gated channels and G-protein coupled receptors.

(RS)-1-{4-[2-(cyclopropylmethoxy)ethyl]-phenoxy}-3-(isopropylamino)propan-2-ol, a drug that binds to and blocks the activation of adrenergic beta-1 receptors.

Betaxolol is a competitive, beta(1)-selective (cardioselective) adrenergic antagonist used to treat hypertension, arrhythmias, coronary heart disease, and glaucoma, and to reduce non-fatal cardiac events in patients with heart failure.

Propranolol is a competitive, nonselective beta-blocker that acts as a beta-adrenergic receptor antagonist without intrinsic sympathomimetic activity.

Ligand-gated ion channels, also known as ionotropic receptors, are trans-membrane proteins consisting of five different units (two α units, one β, one γ, and one δ unit) that form a core with an internal diameter of 0.7 nm. They control the fastest synaptic events by altering channel permeability in response to agonists.

Dihydroergotamine binds with high affinity to 5-HT1Da, 5-HT1Db, 5-HT1A, 5-HT2A, 5-HT2C, noradrenaline α2A, α2B, and dopamine D2L and D3 receptors.

The hormone-responsive element (HRE) is a specific sequence of nuclear DNA that the receptor binding domain recognizes to suppress or promote particular genes.

Nuclear Receptors are a class of receptors that, upon binding with ligands such as steroid hormones, translocate to the nucleus and regulate gene transcription. Examples include Steroid receptors and Hormone receptors.

A region of a receptor that binds growth factors and initiates signaling pathways involved in cell growth and differentiation.

The mechanism by which catecholamines are reabsorbed into presynaptic neurons after being released, primarily through the norepinephrine transporter (NET).

Dopamine is used in the treatment of very low blood pressure, symptomatic slow heart rate, and cardiac arrest if epinephrine is not available.

Isoproterenol is a β1 and β2 adrenoreceptor agonist with almost no activity against alpha adrenergic receptors, used to treat heart block, cardiac arrest, bronchospasm during anesthesia, and various shock states.

Bitolterol is unique in that it is a prodrug, meaning it must first be metabolized by the body before it becomes active.

GPCRs are receptors that are coupled to a G-protein and can bind to GTP, consisting of a polypeptide chain with seven trans-membrane α-helices, an extracellular N-terminal domain for agonist binding, and an internal C-terminal for signal transduction.

Changing the furan ring in prazosin to a tetrahydrofuran ring (as in alfuzosin) greatly increases the half-life, allowing for once-a-day dosing.

Oxymetazoline is an adrenergic alpha-agonist, a direct acting sympathomimetic used as a vasoconstrictor to relieve nasal congestion by constricting smaller arterioles in the nasal passages.

A G-protein consists of three proteins: α, β, and γ, with the α-subunit having enzymatic activity to catalyze the conversion of GTP to GDP.

It is used to terminate supraventricular tachycardia, episodic atrial fibrillation or flutter, arrhythmia during anaesthesia, to reduce heart rate and blood pressure during and after cardiac surgery, and in early treatment of myocardial infarction.

Dimerisation of a pair of receptors is a crucial step in signal transduction for Kinase-linked receptors, followed by auto phosphorylation of tyrosine residues.

Betaxolol blocks beta(1)-receptors, which are mainly located in the heart, leading to a decrease in heart rate and blood pressure, thus reducing oxygen consumption by the heart.

In ligand-gated ion channels, the increased influx of Na+ ions depolarizes the neuron, generating an action potential, particularly in response to excitatory neurotransmitters like acetylcholine.

The levo-isomer of Propranolol is responsible for its adrenergic blocking activity.

Upon binding of a steroid, the receptor undergoes a configurational change, forming a receptor dimer that can recognize specific DNA sequences.

The process by which two receptor molecules bind together, often leading to activation of their intracellular signaling domains.

The biochemical breakdown of catecholamines, primarily through enzymatic processes involving monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT).

Methyldopa is a competitive inhibitor of the enzyme DOPA decarboxylase, leading to reduced dopaminergic and adrenergic neurotransmission in the peripheral nervous system.

Isoproterenol is used to treat heart block, episodes of Adams-Stokes syndrome, cardiac arrest, bronchospasm during anesthesia, and as an adjunct in treating hypovolemic shock, septic shock, low cardiac output states, congestive heart failure, and cardiogenic shock.

Naphazoline is a direct acting sympathomimetic adrenergic alpha-agonist used to induce systemic vasoconstriction, decreasing nasal congestion and constricting around the conjunctiva.

GPCRs can be classified into two categories based on the type of ligand: non-peptide ligands (such as α- and β-adrenergic, dopaminergic, histaminergic, and muscarinic cholinergic receptors) and peptide ligands (such as angiotensin, bradykinin, FSH, LH, TRH, TSH, and thromboxane).

A structural conformational change occurs in the receptor, causing it to acquire high affinity for the αβγ-trimer, leading to the dissociation of GDP and its replacement by GTP.

Oxymetazoline elicits a prolonged decongesting effect (up to 12 hours) by causing vasoconstriction of superficial conjunctival blood vessels and smaller arterioles in the nasal passages.

Silodosin is the most selective for α-1A receptors.

Activated tyrosine residues in Kinase-linked receptors serve as high-affinity binding sites for SH2 domains of various intracellular proteins, facilitating further intracellular signaling.

Inhibitory neurotransmitters like GABA increase chloride ion permeability in ligand-gated ion channels, leading to hyperpolarization of neurons.

1-[4-(2-methoxyethyl)phenoxy]-3-(propan-2-ylamino)propan-2-ol, a selective β1 receptor blocker used to treat high blood pressure and conditions involving an abnormally fast heart rate.

Bisoprolol is a competitive, cardioselective β1-adrenergic antagonist used to lower heart rate and blood pressure, thereby reducing the workload on the heart and oxygen demands.

Propranolol is a racemic compound.

Steroid receptor interaction leads to an increase in RNA polymerase activity and the production of specific mRNA within minutes.

A process where a receptor phosphorylates its own tyrosine residues, which is crucial for activating downstream signaling pathways.

Methyldopa is used to treat hypertension and gestational hypertension.

Terbutaline is a relatively selective beta2-adrenergic bronchodilator that primarily stimulates beta2 receptors in bronchial, vascular, and uterine smooth muscles.

Indirect-acting agents are drugs that do not interact directly with receptors but instead increase the levels of endogenous catecholamines through mechanisms such as MAOIs, COMT inhibitors, release stimulants, and reuptake inhibitors.

Naphazoline is used to decrease nasal congestion and induce constriction around the conjunctiva, as well as to decrease itching and irritation of the eyes.

The C-terminal of GPCRs is responsible for carrying out signal transduction by coupling with a G-protein that can bind to GTP.

The βγ subunit can also activate target proteins, in addition to the α−GTP subunit.

Xylometazoline is a direct acting sympathomimetic adrenergic alpha-agonist used to induce systemic vasoconstriction, thereby decreasing nasal congestion.

The two important pathways are the Ras/Raf/MAP kinase pathway, which is crucial for cell division, growth, and differentiation, and the Jak/Stat pathway, activated by many cytokines to control the synthesis of inflammatory mediators.

TM 4 is one of the four trans-membrane proteins in ligand-gated ion channels and resides on the inner wall of the channel. Its structural change alters channel permeability in response to agonists.

Piperazine is present in prazosin, terazosin, and doxazosin, contributing to the non-selective inhibition of α-1 receptors.

Bisoprolol lowers heart rate and blood pressure by blocking β1-receptors, which are activated by epinephrine, thus helping to manage ischemic heart disease.

It is used to treat high blood pressure, chest pain due to poor blood flow to the heart, prevent further heart problems after myocardial infarction, and to prevent migraines.

Most nuclear receptors are located inside the nucleus of the cell.

Norepinephrine is a naturally occurring catecholamine that directly stimulates adrenergic receptors, causing vasoconstriction and increased myocardial contractility.

Grb2 is an adaptor protein that binds to phosphorylated tyrosine residues on activated receptors, facilitating the recruitment of other signaling proteins.

Terbutaline is used to relax smooth muscle, inhibit uterine contractions, and may cause some cardiostimulatory effects and CNS stimulation.

Hydroxyamphetamine is an indirect-acting sympathomimetic amine that stimulates the release of norepinephrine from postganglionic adrenergic nerves, leading to stimulation of both alpha and beta adrenergic receptors.

GDP is a nucleotide that is exchanged for GTP upon receptor activation, playing a crucial role in the signaling mechanism of GPCRs.

The sympathomimetic action of xylometazoline produces a prolonged decongesting effect lasting 8-12 hours.

Kinase-linked receptors are involved in controlling cellular growth and differentiation, and they also regulate gene transcription indirectly.

The process is terminated by the hydrolysis of GTP into GDP through the GTPase activity of the α−subunit, which is regulated by the target protein.

They are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.

Stimulation of α-1 receptors causes constriction of the radial smooth muscle of the iris, arteries, arterioles, veins, urinary bladder, and the sphincter of the gastrointestinal tract.

The SH2-domain allows proteins like Grb2 to bind specifically to phosphorylated tyrosine residues on receptors, playing a key role in signal transduction.

Metipranolol is a beta1 and beta2 (non-selective) adrenergic receptor-blocking agent indicated for the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.

Local alpha stimulatory effects of Hydroxyamphetamine include dilation of the pupil, increased flow of aqueous humor, and vasoconstriction, while beta stimulatory effects include relaxation of the ciliary muscle and decreased production of aqueous humor.

Targets include adenylate cyclase (for cAMP formation), phospholipase C (for inositol phosphate and diacylglycerol formation), and ion channels (particularly K+ and Ca2+ ions).

The presence of an aromatic ring is essential for the function of a β-blocker, as it is a mandatory structural component.

An enzyme that catalyzes the conversion of L-Tyrosine to Dihydroxyphenylalanine (DOPA) in the biosynthesis of catecholamines.

Stimulation of β-1 receptors increases myocardial contractility, heart rate, automaticity, and atrioventricular (AV) conduction.

Jak is a kinase that associates with cytokine receptors and is activated upon receptor dimerization, leading to phosphorylation of downstream signaling proteins.

Metipranolol is used to reduce intraocular pressure with little or no effect on pupil size or accommodation.

Pseudoephedrine is a sympathomimetic agent used to relieve nasal and sinus congestion, which displaces norepinephrine from storage vesicles in presynaptic neurons, stimulating primarily alpha-adrenergic receptors.

β-Ethanolamine is a crucial component that must be included in the structure of a β-blocker for its activity.

An enzyme that converts Dihydroxyphenylalanine (DOPA) into Dopamine by removing a carboxyl group.

Norepinephrine is used in the treatment of hypotension and during cardiopulmonary resuscitation.

Stat proteins are transcription factors that, once phosphorylated by Jak, translocate to the nucleus to regulate gene expression.

Atenolol is a competitive beta(1)-selective adrenergic antagonist with the lowest lipid solubility in its drug class.

Pseudoephedrine works by displacing norepinephrine from storage vesicles, releasing it into neuronal synapses where it stimulates alpha-adrenergic receptors, resulting in vasoconstriction and decreased nasal and sinus congestion.

The general rule for aromatic substitution is ortho > meta > para, with large para-substituents usually decreasing activity, while large ortho-groups retain some activity.

A catecholamine neurotransmitter synthesized from Dihydroxyphenylalanine (DOPA), involved in reward and motor control.

Epinephrine is a catecholamine that directly stimulates both alpha- and beta-adrenergic systems, causing systemic vasoconstriction and bronchodilation.

Atenolol is used alone or with chlorthalidone in the management of hypertension and edema.

Alkyl substituents on the α, β, or γ carbon lower beta blockade, especially at the α carbon.

An amino acid that serves as a precursor for the synthesis of catecholamines, including DOPA and Dopamine.

Epinephrine is used in the treatment of respiratory distress, status asthmaticus, cardiac arrest, shock, as a styptic to stop bleeding, and to delay absorption of local anesthetics.

The R1 group can only be a secondary substitution, with branched substituents being the optimal choice for activity.

A precursor in the biosynthesis of catecholamines, formed from L-Tyrosine by the action of Tyrosine hydrolase.

Polysubstitution on carbon 2 and 6 makes the compound inactive, while substitution on carbon 3 and 5 retains some activity.

An enzyme that converts Dopamine into Noradrenaline by adding a hydroxyl group.

All the β-blockade is attributed to the (S)-aryloxypropylamine and (R)-ethanolamine isomer.

A catecholamine neurotransmitter synthesized from Dopamine, involved in the body's stress response.

An enzyme that catalyzes the final step in the biosynthesis of Adrenaline from Noradrenaline by adding a methyl group.

A catecholamine hormone produced from Noradrenaline, involved in the fight-or-flight response.

The adrenergic nervous system is the system that uses adrenaline (epinephrine) or nor-adrenaline (nor-epinephrine) as neurotransmitters in the post-synaptic neurons.

Adreno mimetic agents are those that mimic the effect of adrenaline or augment its effects.

Sympatho-lytic agents are those that antagonize the effects of adrenergic action.

The two types of adrenergic receptors are α (alpha) and β (beta), both of which are G-protein coupled receptors.

α1 adrenergic receptors act through the activation of IP3 and DAG.

α2 adrenergic receptors act through lowering cAMP levels.

β1 adrenergic receptors increase cAMP levels.

β2 adrenergic receptors decrease cAMP levels.

Directly acting adrenergic agonists include substances like epinephrine and nor-epinephrine that directly stimulate adrenergic receptors.

Indirectly acting adrenergic agonists include substances like tyramine and phentermine that increase the release of norepinephrine.

α-adrenergic blockers are antagonists that inhibit the action of α-adrenergic receptors, examples include phentolamine and tolazoline.

β-adrenergic blockers are antagonists that inhibit the action of β-adrenergic receptors, examples include propranolol and practlol.