Autonomic Nervous System II

Plants that affect the sympathetic nervous system

Ganglionic blocking compounds

nicotine, lobeline

Peripheral Nervous System: Neurotransmitters & Receptors

CNS

nicotinic receptor

nicotinic receptor

muscarinic receptor

adrenergic receptor

Sympathetic

Parasympathetic

Somatic Motor

nicotinic and muscarinic receptors = cholinergic receptors

Ganglionic Blocking Compounds

• A high dose of nicotine or lobeline (nicotinic cholinergic receptor agonists) can overstimulate ganglionic receptors

• persistent depolarization of autonomic ganglia: autonomic ganglionic blocade

• triggers further release of epinephrine by adrenal medulla, which leads to vasoconstriction and potentiation of ganglionic blockade

Ganglionic Blocking Compounds

Two phases of autonomic ganglionic blocade:• Stimulatory phase:– constriction of capillaries and arterioles– increase in blood pressure– sweating

• Paralytic phase:– decrease in blood pressure…40 mg of nicotine (amount extracted from 2

cigarettes) can cause fatal ganglionic blocade if it is injected (when smoked most nicotine is degraded)

Nicotiana tabacum

Nicotiana tabacum

• Common name: tobacco• Origin: South America• Ethnomedical uses by

Native Americans:• leaves smoked and snorted

as sacred enebriant and CNS stimulant

Nicotiana tabacum

• Active compound: nicotine (alkaloid)

• Mechanisms of action:– CNS stimulant– stimulates acetylcholine

release in autonomic ganglia at juncture of pre- and post-ganglionic neurons

• Therapeutic uses of nicotine (not recommended due to the addictive nature of nicotine)– enhancement of athletic performance– improvement of short-term memory / mental

functioning

Nicotiana tabacum

Lobelia inflata

Lobelia inflata• Common name: Indian

tobacco• Plant family: Lobeliacae• Origin: North America• Habit: herbaceous plant on

forest floor• Ethnomedical uses by

Native Americans:• leaves used as a

respiratory expectorant and for chest conditions

Lobelia inflata

• Active compound: α-lobeline (alkaloid)

• Therapeutic uses:– expectorant– decongestant– smoking deterrant

(stimulates same receptors, but has a milder effect than nicotine)

Compounds That Target the Sympathetic Nervous System

Sympathetic Nervous System (Review)

• Catabolic system that expends (burns) energy• Nerves in this system originate from the thoraco-

lumbar regions• “Fight or flight” responses to danger:– increase in heart rate & force of ventricular contractions– shunting blood to muscles and heart– increase in sweat gland secretion– dilates pupils– dilates bronchial tubes– inhibits GI motility and secretions, contracts GI sphincters– stimulates secretion of adrenaline from adrenal medulla

Sympathetic Nervous System Adrenergic Receptors (Stimulated by Norepinephrine)

• alpha receptors – – reduce glandular secretions– reduce GI motility – increase constriction of certain arterioles and veins

• beta receptors – – increase heart rate, contractions– increase kidney renin secretion– relax trachea and bronchioles – dilate some arterioles and veins (not in skin or brain)– increase breakdown of glycogen / fats for energy

Adrenergic Agonists

Endogenous agonists of α and β adrenergic receptors:

• Epinephrine (adrenaline)– produced by adrenal medulla– released in increased amounts in response to stress– stimulates heart– dilates blood vessels going to skeletal muscle

• Norepinephrine– postganglionic adrenergic neurotransmitter– stimulates heart– constricts blood vessels in skin, mucosal surfaces, and

kidneys

Plant-Derived Adrenergic Agonists(Sympathomimetics)

• Ephedra• Citrus aurantia

Ephedra spp.

Ephedra spp.• Common names: Ephedra, Mormon tea, Ma

Huang• Plant family: Ephedraceae• Plant parts used: aerial parts• Ethnomedical uses: asthma, sinusitis, stimulant• Active compound: ephedrine (alkaloid)– stimulates both α and β receptors– releases stored catecholamines (epinephrine,

norepinephrine, and dopamine)– CNS stimulant– Bronchodilator

Ephedra spp.Chemical derivatives of ephedrine:• pseudoephedrine HCl (sudafed, isophedrine)– vasoconstrictor– decongestant– longer bronchial effect & less CNS stimulation than

ephedrine• phenylpropanolamine– vasoconstrictor– decongestant

• vaponephrine– bronchiodilator to treat asthma

• salbutamol (albuterol, proventil)– bronchodilator to treat asthma

Citrus aurantium (bitter orange)

Citrus aurantium (bitter orange)

• contains synephrine alkaloids and para-octopamine (typically cited as active ingredients)

• these compounds have α-adrenergic agonist properties, and may also stimulate β receptors in the sympathetic nervous system

Citrus aurantium (bitter orange)

• effects similar to Ephedra• often added to herbal weight loss

supplements (in place of banned Ephedra)• compound responsible for weight loss is most

likely para-synephrine, also called oxedrine

Anti-adrenergic Compounds

• Ephedrine chemical derivatives are also used to create postsynaptic adrenergic receptor blockade

• used to treat hypertensiontwo classes:• β1 receptor specific competitive blockers– lopressor & tenormin

• β1β2 receptor competitive blockers– corgard, timoptic (also treats glaucoma)

Other plant-derived adrenergic antagonists

• Rauvolfia serpentina• Pausinystalia johimbe

Rauvolfia serpentina

Rauvolfia serpentina

• Plant family: Apocynaceae• Origin: India, Indomalasia• Habit: climbing shrub• Plant part used: root• Ethnomedical uses in Ayurvedic medicine:– sedative– tranquilizer– antipsychotic– antihypertensive

Rauvolfia serpentina

• Active compounds:– reserpine, rescinnamine, ajmalicine

• Mechanism of action:– binds storage vesicles in peripheral and central

adrenergic neurons– dysfunctional storage vesicles cause nerve endings

to lose their ability to concentrate and store catecholamines (norepinephrine and dopamine)

– has similar effect on serotonin (in CNS)

Rauvolfia serpentina

Physiological effects of reserpine:

• reduced sympathetic effects

• reduced catecholamine levels in CNS, heart, and PNS

• reduced serotonin levels• lowered blood pressure

due to reduced norephinephrine levels

Rauvolfia serpentina

Therapeutic uses:• reserpine & rescinnamine – treat psychosis, mania and

hypertension

• ajmalicine– treats circulatory disorders

Pausinystalia johimbe

• Common name: yohimbe• Plant family: Rubiaceae• Origin: West Africa• Active compound: Yohimbine• Plant part used: bark

Pausinystalia johimbe• Ethnomedical uses: taken orally as an

aphrodisiac in West Africa by many different ethnolinguistic groups

• Mechanism of action: Yohimbine causes competitive blockade on adrenergic receptors

• Has highest affinity for α2 receptors

• Therapeutic use: yohimbine taken orally as an aphrodisiac and to treat impotence