Section 6 - (PT2) Drugs Affecting the Autonomic Nervous System

Principles of Pharmacology and Toxicology (BIOL3020) Noradernergic Transmission Adrenaline Biosynthesis w Adrenaline Biosynthesis Noradernergic Neuron Noradrenaline is then transported to vesicles Vesicles are loaded by transporters Drugs such as reserpine block this transport and cause nerve terminals to become depleted of NA. Used to treat hypertension Noradernergic Neuron NA is also taken up by both presynaptic neuron and post synaptic cell Uptake transporters can be inhibited by drugs NA is metabolized by monoamine oxidase (MAO) MAO inhibitors treat depression Noradernergic Receptors Drugs that effect Adrenoreceptors Drugs that effect other adrenoreceptors Drugs Affecting Noradrenergic Transmission Some General Rules Smooth muscle contraction is via activation of Phospholipase C Cardiac muscle contraction is via Adenylate Cyclase activation This opposes the action of the M2 mAChR that inhibits AC In Smooth muscle activation of AC inhibits contraction Click to edit Master title style Click to edit Master text styles Second level Third level Fourth level Fifth level Click to edit Master title style Click to edit Master subtitle style Action Potential Na Target Cell acetylcholine Preganglionic neuron Postganglionic neuron AKA Noradrenergic Neuron Nicotinic acetylcholine receptor Depolarization and possible Action Potential noradrenaline Sympathetic System Pre Synaptic Nerve terminal NA NA NA Reserpine NA NA Cocaine amphetamines Post Synaptic Cell U1 NA Metabolite MAO U2 MAO inhibitors Normetan- ephrine GP PLC IP3 Ca2 Ca2 Ca2 NA Contraction ER or SR 1 Activate PLC and increase IP3 Involved in smooth muscle contraction vasoconstriction (Stimulatory) NA GP AC 1 PK Ca2 Ca2 cAMP Contraction Activate AC and increase cAMP formation Increase heart rate and force of contraction (Stimulatory) NA GP AC 2 PK cAMP Acts to reduce muscle contraction Activate AC and increase cAMP formation In smooth muscle, cAMP activates enzymes (protein kinase) that reduce contraction (Inhibitory) GP PLC IP3 Ca2 Ca2 Ca2 Lig Contraction ER or SR NA GP AC 1 PK Ca2 Ca2 cAMP NA GP AC 2 PK cAMP Acts to reduce muscle contraction Principles of Pharmacology and Toxicology (BIOL3020) Noradernergic Transmission Adrenaline Biosynthesis Adrenaline Biosynthesis Noradernergic Neuron Noradrenaline is then transported to vesicles Vesicles are loaded by transporters Drugs such as reserpine block this transport and cause nerve terminals to become depleted of NA. Used to treat hypertension Noradernergic Neuron NA is also taken up by both presynaptic neuron and post synaptic cell Uptake transporters can be inhibited by drugs NA is metabolized by monoamine oxidase (MAO) MAO inhibitors treat depression Noradernergic Receptors Drugs that effect Adrenoreceptors Drugs that effect other adrenoreceptors Drugs Affecting Noradrenergic Transmission Principles of Pharmacology and Toxicology (BIOL3020) Noradernergic Transmission Adrenaline Biosynthesis Adrenaline Biosynthesis Noradernergic Neuron Noradrenaline is then transported to vesicles Vesicles are loaded by transporters Drugs such as reserpine block this transport and cause nerve terminals to become depleted of NA. Used to treat hypertension Noradernergic Neuron NA is also taken up by both presynaptic neuron and post synaptic cell Uptake transporters can be inhibited by drugs NA is metabolized by monoamine oxidase (MAO) MAO inhibitors treat depression Noradernergic Receptors Drugs that effect Adrenoreceptors Drugs that effect other adrenoreceptors Drugs Affecting Noradrenergic Transmission Some General Rules Smooth muscle contraction is via activation of Phospholipase C Cardiac muscle contraction is via Adenylate Cyclase activation This opposes the action of the M2 mAChR that inhibits AC In Smooth muscle activation of AC inhibits contraction . Smooth muscle contraction is via activation of Phospholipase C Cardiac muscle contraction is via Adenylate Cyclase activation This opposes the action of the M2 mAChR that inhibits AC In Smooth muscle activation of AC inhibits contraction GP PLC IP3 Ca2 Ca2 Ca2 NA Contraction ER or SR 1 Activate PLC and increase IP3 Involved in smooth muscle contraction vasoconstriction (Stimulatory) 3 Principles of Pharmacology and Toxicology (BIOL3020) Noradernergic Transmission Adrenaline Biosynthesis Adrenaline Biosynthesis Noradernergic Neuron Noradrenaline is then transported to vesicles Vesicles are loaded by transporters Drugs such as reserpine block this transport and cause nerve terminals to become depleted of NA. Used to treat hypertension Noradernergic Neuron NA is also taken up by both presynaptic neuron and post synaptic cell Uptake transporters can be inhibited by drugs NA is metabolized by monoamine oxidase (MAO) MAO inhibitors treat depression Noradernergic Receptors Drugs that effect Adrenoreceptors Drugs that effect other adrenoreceptors Putting it together Drugs Affecting Noradrenergic Transmission Some General Rules Smooth muscle contraction is via activation of Phospholipase C Cardiac muscle contraction is via Adenylate Cyclase activation This opposes the action of the M2 mAChR that inhibits AC In Smooth muscle activation of AC inhibits contraction @ Principles of Pharmacology and Toxicology (BIOL3020) Noradernergic Transmission Adrenaline Biosynthesis Adrenaline Biosynthesis Noradernergic Neuron Noradrenaline is then transported to vesicles Vesicles are loaded by transporters Drugs such as reserpine block this transport and cause nerve terminals to become depleted of NA. Used to treat hypertension Noradernergic Neuron NA is also taken up by both presynaptic neuron and post synaptic cell Uptake transporters can be inhibited by drugs NA is metabolized by monoamine oxidase (MAO) MAO inhibitors treat depression Noradernergic Receptors Drugs that effect Adrenoreceptors Drugs that effect other adrenoreceptors Putting it together Drugs Affecting Noradrenergic Transmission Some General Rules Smooth muscle contraction is via activation of Phospholipase C Cardiac muscle contraction is via Adenylate Cyclase activation This opposes the action of the M2 mAChR that inhibits AC In Smooth muscle activation of AC inhibits contraction NA GP AC 2 PK cAMP Acts to reduce muscle contraction Principles of Pharmacology and Toxicology (BIOL3020) Noradernergic Transmission Adrenaline Biosynthesis Adrenaline Biosynthesis Noradernergic Neuron Noradrenaline is then transported to vesicles Vesicles are loaded by transporters Drugs such as reserpine block this transport and cause nerve terminals to become depleted of NA. Used to treat hypertension Noradernergic Neuron NA is also taken up by both presynaptic neuron and post synaptic cell Uptake transporters can be inhibited by drugs NA is metabolized by monoamine oxidase (MAO) MAO inhibitors treat depression Noradernergic Receptors Drugs that effect Adrenoreceptors Drugs that effect other adrenoreceptors Putting it together Drugs Affecting Noradrenergic Transmission Some General Rules Smooth muscle contraction is via activation of Phospholipase C Cardiac muscle contraction is via Adenylate Cyclase activation This opposes the action of the M2 mAChR that inhibits AC In Smooth muscle activation of AC inhibits contraction NA GP AC 2 PK cAMP Acts to relax SM Principles of Pharmacology and Toxicology (BIOL3020) Noradernergic Transmission Adrenaline Biosynthesis Adrenaline Biosynthesis Noradernergic Neuron Noradrenaline is then transported to vesicles Vesicles are loaded by transporters Drugs such as reserpine block this transport and cause nerve terminals to become depleted of NA. Used to treat hypertension Noradernergic Neuron NA is also taken up by both presynaptic neuron and post synaptic cell Uptake transporters can be inhibited by drugs NA is metabolized by monoamine oxidase (MAO) MAO inhibitors treat depression Noradernergic Receptors Drugs that effect Adrenoreceptors Drugs that effect other adrenoreceptors Putting it together Drugs Affecting Noradrenergic Transmission Some General Rules Smooth muscle contraction is via activation of Phospholipase C Cardiac muscle contraction is via Adenylate Cyclase activation This opposes the action of the M2 mAChR that inhibits AC In Smooth muscle activation of AC inhibits contraction NA GP AC 2 PK cAMP Acts to relax SM Activate AC and increase cAMP formation In smooth muscle, cAMP activates enzymes (protein kinase) that cause SM relaxation (Inhibitory) 3 Principles of Pharmacology and Toxicology (BIOL3020) Noradernergic Transmission Adrenaline Biosynthesis Adrenaline Biosynthesis Noradernergic Neuron Noradrenaline is then transported to vesicles Vesicles are loaded by transporters Drugs such as reserpine block this transport and cause nerve terminals to become depleted of NA. Used to treat hypertension Noradernergic Neuron NA is also taken up by both presynaptic neuron and post synaptic cell Uptake transporters can be inhibited by drugs NA is metabolized by monoamine oxidase (MAO) MAO inhibitors treat depression Noradernergic Receptors Drugs that effect Adrenoreceptors Drugs that effect other adrenoreceptors Putting it together Drugs Affecting Noradrenergic Transmission Some General Rules Smooth muscle contraction is via activation of Phospholipase C Cardiac muscle contraction is via Adenylate Cyclase activation This opposes the action of the M2 mAChR that inhibits AC In Smooth muscle activation of AC inhibits contraction Pre Synaptic Nerve terminal NA NA NA Reserpine 0 Principles of Pharmacology and Toxicology (BIOL3020) Noradernergic Transmission Adrenaline Biosynthesis Adrenaline Biosynthesis Noradernergic Neuron Noradrenaline is then transported to vesicles Vesicles are loaded by transporters Drugs such as reserpine block this transport and cause nerve terminals to become depleted of NA. Used to treat hypertension Noradernergic Neuron NA is also taken up by both presynaptic neuron and post synaptic cell Uptake transporters can be inhibited by drugs NA is metabolized by monoamine oxidase (MAO) MAO inhibitors treat depression Noradernergic Receptors Drugs that effect Adrenoreceptors Drugs that effect other adrenoreceptors Putting it together Drugs Affecting Noradrenergic Transmission Some General Rules Smooth muscle contraction is via activation of Phospholipase C Cardiac muscle contraction is via Adenylate Cyclase activation This opposes the action of the M2 mAChR that inhibits AC In Smooth muscle activation of AC inhibits contraction 0