Autonomic Nervous System II

1. Autonomic Nervous System II Plants that affect the sympathetic nervous system

2. Ganglionic blocking compounds nicotine, lobeline

3. Peripheral Nervous System: Neurotransmitters & Receptors CNS Sympathetic adrenergic receptor nicotinic receptor Parasympathetic muscarinic receptor Somatic Motor nicotinic receptor nicotinic and muscarinic receptors = cholinergic receptors

4. 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

5. 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)

6. Nicotiana tabacum

7. Nicotiana tabacum • Common name: tobacco • Origin: South America • Ethnomedical uses by Native Americans: • leaves smoked and snorted as sacred enebriant and CNS stimulant

8. 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

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

10. Lobelia inflata

11. 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

12. Lobelia inflata • Active compound: α-lobeline (alkaloid) • Therapeutic uses: • expectorant • decongestant • smoking deterrant (stimulates same receptors, but has a milder effect than nicotine)

13. Compounds That Target the Sympathetic Nervous System

14. 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

15. 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

16. 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

17. Plant-Derived Adrenergic Agonists(Sympathomimetics) • Ephedra • Citrus aurantia

18. Ephedra spp.

19. 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

20. 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

21. Citrus aurantium (bitter orange)

22. 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

23. 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

24. Anti-adrenergic Compounds • Ephedrine chemical derivatives are also used to create postsynaptic adrenergic receptor blockade • used to treat hypertension two classes: • β1 receptor specific competitive blockers • lopressor & tenormin • β1β2 receptor competitive blockers • corgard, timoptic (also treats glaucoma)

25. Other plant-derived adrenergic antagonists • Rauvolfia serpentina • Pausinystalia johimbe

26. Rauvolfia serpentina

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

28. 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)

29. 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

30. Rauvolfia serpentina Therapeutic uses: • reserpine & rescinnamine • treat psychosis, mania and hypertension • ajmalicine • treats circulatory disorders

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

32. 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