Transcript Plant Drugs of the Autonomic Nervous System II

Autonomic Nervous System II
Plants that affect the sympathetic
nervous system
Ganglionic blocking compounds
nicotine, lobeline
Peripheral Nervous System:
Neurotransmitters & Receptors
CNS
Sympathetic
nicotinic receptor
adrenergic receptor
Parasympathetic
muscarinic receptor
Somatic Motor
nicotinic receptor
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 preand post-ganglionic neurons
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
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: αlobeline (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 thoracolumbar 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 paraoctopamine (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 hypertension
two 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