Adrenergic Agonists Quiz

Adrenergic Agonists

• Adrenergic drugs affect receptors stimulated by norepinephrine (noradrenaline) or epinephrine (adrenaline), known as adrenergic receptors or adrenoceptors.
• Adrenergic drugs that activate adrenergic receptors are termed sympathomimetics, and drugs that block the activation of adrenergic receptors are termed sympatholytics.

Catecholamines

• Catecholamines are compounds containing a catechol moiety (a benzene ring with two adjacent hydroxyl groups) and an amine side chain.
• The most important catecholamines are:
  • Noradrenaline (norepinephrine), a transmitter released by sympathetic nerve terminals.
  • Adrenaline (epinephrine), a hormone secreted by the adrenal medulla.
  • Dopamine, the metabolic precursor of noradrenaline and adrenaline, also a transmitter/neuromodulator in the central nervous system.
  • Isoprenaline (isoproterenol), a synthetic derivative of noradrenaline, not present in the body.

Adrenergic Neurons

• Adrenergic neurons release norepinephrine as the primary neurotransmitter.
• These neurons are found in the central nervous system (CNS) and also in the sympathetic nervous system, where they serve as links between ganglia and the effector organs.

Neurotransmission

• Neurotransmission in adrenergic neurons involves the following steps: synthesis, storage, release, and receptor binding of norepinephrine, followed by removal of the neurotransmitter from the synaptic gap.
• Synthesis of norepinephrine:
  • Tyrosine is transported into the adrenergic neuron and hydroxylated to dihydroxyphenylalanine (DOPA) by tyrosine hydroxylase.
  • DOPA is then decarboxylated to form dopamine by aromatic L-amino acid decarboxylase.
• Storage of norepinephrine in vesicles:
  • Dopamine is transported into synaptic vesicles by an amine transporter system.
  • Dopamine is hydroxylated to form norepinephrine by dopamine β-hydroxylase.
• Release of norepinephrine:
  • An action potential triggers an influx of calcium ions, causing synaptic vesicles to fuse with the cell membrane and release their contents into the synapse.
• Binding to receptors:
  • Norepinephrine released from the synaptic vesicles binds to postsynaptic receptors on the effector organ or to presynaptic receptors on the nerve ending.

Adrenergic Receptors

• Adrenergic receptors are classified into two main families: α and β receptors.
• α-Adrenoceptors:
  • Show a weak response to isoproterenol, but are responsive to naturally occurring catecholamines epinephrine and norepinephrine.
  • Subdivided into two subgroups, α1 and α2, based on their affinities for α agonists and blocking drugs.
• α1 Receptors:
  • Present on the postsynaptic membrane of the effector organs and mediate many of the classic effects, originally designated as α-adrenergic, involving constriction of smooth muscle.
  • Activation of α1 receptors initiates a series of reactions through the G protein activation of phospholipase C, ultimately resulting in the generation of second messengers inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG).
• α2 Receptors:
  • Located primarily on sympathetic presynaptic nerve endings and control the release of norepinephrine.
  • Stimulation of α2 receptors causes feedback inhibition and inhibits further release of norepinephrine from the stimulated adrenergic neuron.
• β-Adrenoceptors:
  • Responses differ from those of α receptors and are characterized by a strong response to isoproterenol, with less sensitivity to epinephrine and norepinephrine.
  • Subdivided into three major subgroups, β1, β2, and β3, based on their affinities for adrenergic agonists and antagonists.