Pharmacology of Adrenergic and Cholinergic Receptors

Adrenergic Receptors and Neurotransmission

• Adrenergic receptors are classified into two types: alpha (α) and beta (β)
• α receptors: NA > A > Isoprenaline
• β receptors: Isoprenaline > A > NA
• α receptors are further divided into α1 and α2, and β receptors into β1, β2, and β3
• Each subtype has a different second messenger response

Neurotransmitter Release and Re-uptake

• Neurotransmitter release: ACh, NA, tyramine, ephedrine, and amphetamine promote release
• Re-uptake inhibitors: cocaine, imipramine; inhibit uptake 1, increase NA effect
• Uses: cocaine (local anaesthetic), imipramine (depression)
• Side effects: cocaine (drug dependence), imipramine (atropine-like effects)

Inhibitors of Enzymatic Inactivation

• ACh esterase inhibitors: galanthamine; inhibit ACh esterase in synaptic cleft, prolong ACh action
• MAO inhibitors: phenelzine; inhibit monoamine oxidase in presynaptic terminal, increase stored pool
• Uses: galanthamine (Alzheimer's disease), phenelzine (depression)
• Side effects: phenelzine (cheese reaction)

Adrenergic Transmission and Receptors

• Noradrenaline receptors: α1, α2, β1, β2, β3
• α1: inositol triphosphate (IP3), diacylglycerol (DAG)
• α2: ↓ cAMP
• β1: ↑ cAMP
• β2: ↑ cAMP
• β3: unknown

Structure-Activity Relationships (SAR)

• Increase size of substituents on N atom: potent β agonists, less affinity for UT1 and MAO
• Addition of α-methyl group: α selective, resistant to MAO, still susceptible to UT1
• Removal of β -OH: greatly reduced interaction with α and β receptors
• Substitute or replace catechol -OH groups: not degraded by COMT, still susceptible to UT1

Adrenergic Receptors in Peripheral Tissues

• Cardiovascular system: α receptors (smooth muscle contraction), β receptors (smooth muscle relaxation)
• Heart: β1 receptors (+ve chronotrophic and inotrophic effects)
• Eye: α receptors (radial papillary dilation muscle), β receptors (ciliary muscle relaxation)
• Respiratory tract: β2 receptors (bronchial muscle relaxation, bronchodilation)
• Gastrointestinal tract: α receptors (presynaptic on cholinergic terminals, ↓ release of ACh), β receptors (smooth muscle relaxation)

Adrenergic Agonists and Antagonists

• Receptor agonism (mimics action of NorAdr): NorAdr, α phenylephrine, methoramine (α1), Clonidine, α-methyl-NorAdr (α2), isoprenaline, Adr (β), prenalterol (β1), salbutamol, terbutaline (β2)
• Receptor antagonism (blocks action of NorAdr): atropine (M antagonist), phentolamine (α antagonist), propranolol (β antagonist)