1. Plant Drugs that Affect the Autonomic Nervous System

2. Major Divisions of the Nervous System
Central nervous system (CNS)
brain and spinal column
Peripheral nervous system (PNS)
somatic nervous system: innervates skeletal muscle during voluntary movement (efferent system) & sensory nerve endings for touch and pain (afferent system)
Autonomic nervous system (ANS): controls involuntary responses that maintain homeostasis

3. Major Divisions of the Autonomic Nervous System
Sympathetic Nervous System &
Parasympathetic Nervous System
the two systems work antagonistically: inhibition of one system tends to produce effects that resemble the stimulation of the other system

5. Sympathetic Nervous System
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

6. Parasympathetic Nervous System
Anabolic system that promotes the conservation and storage of energy
Nerves in this system originate from the cranial and sacral regions
promotes digestion and storage of food
contracts pupils
stimulates secretion from lacrimal and salivary glands
decreases heart rate and force of ventricular contractions
constricts bronchia and stimulates bronchial gland secretion
stimulates motility and secretion of GI tract
relaxes GI sphincters
contracts bladder

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

9. Sympathetic Nervous System Adrenergic Receptors (Stimulated by Endogenous Norepinephrine)
alpha receptors – reduce glandular secretions, 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 fats to release energy
Epinephrine (adrenaline) – main neurohormone produced by the adrenal medulla – the most potent endogenous stimulator of adrenergic alpha and beta receptors

10. Parasympathetic Nervous System Receptors (Stimulated by Endogenous Acetylcholine)
Nicotinic receptors – are located in the autonomic ganglia of both the sympathetic and parasympathetic systems (and the nerve endings of the somatic motor system)

11. Parasympathetic Nervous System Receptors (Stimulated by Endogenous Acetylcholine)
Muscarinic receptors - are associated with parasympathetic functions and are located at the ends of postganglionic neurons in peripheral tissues (effectors, e.g., glands, smooth muscle) innervated by the parasympathetic system

12. Parasympathetic Nervous System Receptors (Stimulated by Acetylcholine)
Nicotinic receptor - a channel protein that, upon binding by acetylcholine, opens to allow diffusion of cations
Muscarinic receptor - a membrane protein: upon stimulation by neurotransmitter, it causes the opening of ion channels indirectly, through a second messenger. For this reason, the action of a muscarinic synapse is relatively slow.

13. Drugs that affect the autonomic nervous system:
agonists – substances that stimulate receptors
antagonists – substances that block a receptor
drugs that have chemical or molecular resemblance to endogenous neurotransmitters (acetylcholine or norepinephrine) of the ANS can stimulate or inhibit this system

14. Parasympathetic Agonists
Modes of action:
direct agonistic action on the receptor
inactivation of acetylcholinesterase (enzyme that breaks down acetylcholine), resulting in accumulation of acetylcholine in synaptic cleft

15. Muscarinic Cholinergic Receptor Agonists
Acetylcholine (endogenous neurotransmitter)
Synthetic choline esters (methacholine, carbachol, betanechol)
Cholinomimetic plant (and fungal) alkaloids:
muscarine
pilocarpine
arecoline (also affects nicotinic cholinergic receptors)

16. Muscarine compound isolated from various species of fungi:
Amanita muscaria, Amanita spp., Inocybe spp. and Clitocybe spp.
common name: amanita, fly agaric
origin: Siberia, North America
habit: mushroom with red, orange, yellow or cream colored cap with white spots. Grows on forest floor

18. Muscarine, cont. Ethnomedical/cultural uses:
mushroom eaten by Siberian indigenous people as hallucinogen
dried mushrooms repel flies
compounds with hallucinogenic (CNS) activity:
ibotenic acid, muscimole, muscazone
PSN principle active compound: muscarine

19. Muscarine, cont. chemical class: quaternary ammonium alkaloid
chemical derivatives: muscarine  oxotremorine
Muscarine effects: diaphoretic, salivation, lacrimation, vision problems, nausea, vomiting, diarrhea, hypotension, brachycardia, bronchiospasm
Oxotremorine effects: stimulates receptors in basal ganglia and produces parkinsons-like effects (spasticity or tremor)
Modern medical uses: neurobiological research (understanding muscarinic receptors)
Antedote: 1 – 2 mg of atropine IM every 30 min

20. Pilocarpine Isolated from Pilocarpus jaborandi, P. microphyllus
Plant family: Rutaceae (citrus family)
Common name: Jaborandi (means slobber mouth plant in Tupi language)
Origin: lowland wet forests of Tropical America, West Indies
Ethnomedical uses: members of the Tupi culture in Brazil chew leaves to induce salivation and sweating

22. Pilocarpine, cont. Chemical class: tertiary amine alkaloid
Mechanism of action: cholinergic receptor agonist with strong postganglionic (muscarinic receptor) stimulation and mild ganglionic (nicotinic receptor) stimulation
Muscarinic receptor stimulation effects:
salivation
intestinal motility
pupil constriction

23. Pilocarpine, cont. Therapeutic uses:
Topical application to eye constricts pupils
treats open-angle glaucoma by reducing intraocular pressure
Oral administration treats dry mouth (xerostoma)
Also used to reduce side effects of morphine treatment, including:
dry mouth
constipation
urinary retention
Overdose may cause cardiovascular collapse
Antedote is atropine (conversely, pilocarpine is sometimes used as an antedote in cases of atropine poisoning)

24. Arecoline From Areca catechu Plant family: Arecaceae (palm family)
Common name: betelnut, betel, areca nut
Origin: tree in wet forests of S Asia, Indomalaysia, Oceania, probably originally from Sulawesi (Indonesia)
Ethnobotanical use: Used as a masticatory (chew): the areca seed is rolled in leaves of Piper betel and mixed with gambir (a spice made from the boiled leaves of Unicaria gambir) and shell lime (which changes pH to release active compounds)

26. Arecoline, cont. Ethnomedical uses:
euphoretic
cardiac tonic
energizer
antihelminthic
Chemical structure: arecoline is an alkaloid
Chemical derivative: arecoline  aceclidine (glaucoma treatment in Europe)
Arecoline stimulates both muscarinic and nicotinic receptors (in ANS and CNS)

27. Parasympathetic Agonists: Anticholinesterase Compounds
prevent hydrolysis of acetylcholine by acetylcholinesterase at cholinergic transmission sites, resulting in an accumulation of the transmitter
some synthetic compounds with this type of activity include:
insecticides (parathion, malathion)
nerve poisons (sarin, tabun)

28. Physostigmine From Physostigma venemosum
Plant family: Fabaceae (pea or bean family)
Common names: calabar, ordeal, or esere bean
Origin: rainforests of West Africa
Habit: a perennial woody vine (liana)
Cultural origins: used by the Efik people of the Calabar region of SE Nigeria

30. Physostigmine, cont. Ethnomedical uses:
dry beans as ordeal poison in witchcraft trials
perceived ability to “reveal” and “destroy” witchcraft…suspected witch is given a drink of ground up beans in water: if guilty, mouth shakes and mucous comes out of nose (and/or the person dies), if innocent, the suspect will only vomit
beans still carried today for protection against witchcraft

31. Physostigmine, cont. Chemical class: indole alkaloid
Chemical derivatives:
neostigmine
pyridostigmine
edrophonium
demecarium

32. Physostigmine, cont. Mechanism of action:
inhibits acetylcholinesterase in postganglionic nerves & myoneural nerve endings (somatic motor neurons)
Physiological cholinergic effects:
diaphoresis (sweating)
reduced heart rate
smooth muscle stimulation in intestines and bladder

33. Physostigmine, cont.
Modern medical uses of physostigmine and derivatives –
Physostigmine:
glaucoma
antedone for anticholinergic (e.g., atropine) poisoning
Neostigmine, pyridostigmine, demercarium:
intestinal stimulant
treatment of myasthenia gravis (muscle weakness disease with defect in myoneural conduction)
Edrophonium:
used to diagnose and treat myasthenia gravis

35. Intermission

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

37. Antimuscarinic (Anticholinergic) Compounds
Parasympathetic depressants – substances that are muscarinic receptor antagonists
The plant family Solanaceae is the major natural source of antimuscarinic compounds
Tropane alkaloids

38. Solanaceae

40. Antimuscarinic (Anticholinergic) Compounds
Tropane alkaloids from the Solanaceae:
atropine
scopolamine
hyoscyamine

41. Antimuscarinic (Anticholinergic) Compounds
Tropane Alkaloids:
Resemble chemical structure of acetylcholine, but act as antagonists at receptor
Bind to postganglionic parasympathetic receptors and block access of acetylcholine
Interfere or block the normal transmission of postganglionic parasympathetic messages
Also can have a CNS effect (especially scopolamine)
Synthetic muscarinic receptor antagonists include tricyclic antidepressants

42. Atropa belladona

43. Atropa belladonna Common name: belladonna
historically used as a cosmetic to enlarge pupils
also used to poison various Roman emperors
Origin: Europe
Also traditionally used as an:
analgesic
intestinal antispasmodic
hallucinogen (a component of witches “flying ointment” in the Middle Ages in Europe)

44. Atropa belladonna Active compounds: atropine (first isolated in 1831)
anticholinergic at muscarinic receptors
pupil dilator (mydriatic)
cardiac stimulant
Hyoscyamine
analgesic
antispasmodic
Scopolamine
anticholinergic and has CNS effects
pupil dilator
hallucinogen

45. Atropa belladonna
Therapeutic uses of belladonna and its tropane alkaloids:
A. belladonna tincture:
used as an intestinal antispasmodic and analgesic
Scopolamine:
used to dilate pupils, used to treat motion sickness (unfortunate side effect of hallucinations)
Hyoscyamine:
used as an analgesic, sedative, and antispasmodic
Atropine:
used as a pupil dilator, cardiac stimulant, treatment for brachycardia, treatment for organophosphate or insecticide poisoning (counteracts effects of muscarinic agonists)
Lomotil (atropine-diphenoxylate): reduces intestinal motility to treat diarrhea
Atrovent (ipatropium bromide): a bronchodilator used to treat asthma

46. Hyoscyamus niger & H. muticus

47. Hyoscyamus niger & H. muticus
Common name: Henbane
Hyoscyamus niger:
from Eurasia, N. Africa
Hyoscyamus muticus:
from India to Egypt, grown in CA
Habit:
herbaceous plant in open fields and disturbed areas
Plant parts used:
leaves, flower tops (rich in hyoscyamine)
leaves seeds (rich in scopolamine)

48. Hyoscyamus niger & H. muticus
Ethnomedical uses:
used in many cultures in Europe, Egypt, Near East and Asia as an:
antispasmodic
analgesic
mydriatic (pupil dilator)
inebriant / hallucinogen

49. Hyoscyamus niger & H. muticus
Active compounds:
hyoscyamine
anticholinergic at muscarinic receptors
analgesic, sedative, intestinal antispasmodic
scopolamine
anticholinergic, also CNS effects
pupil dilator and treatment for motion sickness

50. Mandragora officinarum

51. Mandragora officinarum
Common name: Mandrake
Origin: Europe to the Himalayas
Habit: herb with thick tuberous roots that sometimes resemble a human
Cultural origins: used by many cultures in Europe and Asia

52. Mandragora officinarum

53. Mandragora officinarum
“The root was to be picked before dawn on a Friday morning by a black dog, then washed and "fed" with milk and honey and, in some prescriptions, blood, whereupon it would fully develop into a miniature human which would guard and protect its owner.”

54. Mandragora officinarum
All parts of plant contain hyoscyamine
Therapeutic uses:
intestinal antispasmodic
analgesic
sedative
used as an anesthetic in surgery until the introduction of ether in the mid 1800s

55. Datura stramonium

56. Datura stramonium Common names:
Algonquin: wysoccan
English: Jimson weed, Jamestown weed, thorn apple
Origin: North America, now naturalized around the world
Habit: herb with erect flowers that grows in open fields and disturbed areas

57. Datura stramonium Ethnomedical uses: leaves, fruits taken orally for:
asthma
sedative
hallucinogen (esp. the seeds)
Algonquins of the eastern US gave wysoccan to boys as a hallucinogen for days in adolescent ceremony…after completion of ceremony, they were considered adults

59. Datura stramonium Active compounds: Scopolamine Hyoscyamine
Therapeutic uses:
pupil dilation, antispasmodic, analgesic

60. other Datura species
Ethnomedical uses: sacred psychogenic & hallucinogen
D. innoxia – sacred hallucinogen in SW US and Mexico
D. ceratocaula – used by Aztecs
D. candida – Colombia & South America
D. metel – native to India, used by Hindu sadhus for spiritual experience…this painting sometimes present in paintings of Shiva

61. Datura innoxia – US Southwest & Mexico

62. Datura ceratocaula – Central America

63. Datura candida – Colombia, South America

64. Datura metel - India

65. Datura metel - India

66. Brugmansia spp. Common name: trumpet flower
Perennial shrubs and trees with pendulous flowers
Chemistry: tropane alkaloids, especially scopolamine
Ethnomedical uses: sacred psychoactive with intense intoxication followed by hallucinations

67. Brugmansia spp.
Brugmansia aurea – different varieties with different hallucinogenic properties are propagated vegetatively by shamans in South America

68. Brugmansia aurea

69. Brugmansia spp.
Brugmansia sanguinea – used as a hallucinogen and medicine by South American cultures from Chile to Colombia

70. Brugmansia sanguinea