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Stimulants

Terms in this set (49)

Stimulant Mechanism of Action
Neurotransmitter activity is regulated, increases the activity of the sympathetic nervous system.
Types of Stimulant Plants
Organized by their mechanism of action.
1) Adrenergic (monoaminergic)
2) Cholinergic
3) Purinergic
(These refer to the type of neuron or neurotransmitter affected by the plant compound). The plants in this lecture are alkaloids.
1) Purinergic Stimulants
Methylxanthines, which are the most widely used stimulants in the world. Stimluate the CNS, like other stimulants. Includes caffeine!
Methylxanthines
Caffeine is one of three closely related methylxanthines (including theophylline and theobromine). These compounds have purinergic activity, meaning they inhibit/activate purine neurotransmitter function. One endogenous neurotransmitter is adenosine.
Methylxanthine Mechanism
Ex: Adenosine --> Endogenous inhibitory neurotransmitter that acts as behavioural sedative. Inhibits release of most neurotransmitters into the synapse.
Caffeine mechanism
Caffeine, similar structure to Adenosine, competes for adenosine receptors, thus inhibiting Adenosine's sedative function.
Differences among Methylxanthines
The methylxanthines, albeit similar, have slightly different functions.
CNS and muscle skeleton stimulants: Caffeine>Theophylline>Theobromine
Cardiovascular stimulants:
Theophylline>Theobromine>Caffeine
Medicinal Uses of Methylxanthines
Historical: reduce lust, measles
Modern: Component of non-prescription pain remedies, theophylline used to treat asthma, as it dilates the bronchioles.
Caffeine most often used for CNS stimulation, and the effects are heightened by carbonation.
Physiological Effects of Caffeine
-Increases basal metabolic rate, heart rate and blood pressure, is a diuretic, stimulates the CNS and skeletal muscles, improves psychomotor performance, and dilates bronchial tubes and coronary arteries.
Negative Effects of Caffeine
Chance of miscarriage doubled when 10oz. taken daily. May develop tolerance, addiction, withdrawal.
Drug Addiction
Caused by brain's rewarding system; is a state of dependance on a drug that involves tolerance and withdrawal systems when the drug is rapidly removed.
Drug Dependance
Psychological: Cravings lead to drug seeking behaviour, despite known risks.
Physiological: Tolerance and withdrawal. Molecular and cellular changes may have occurred due to drug activity.
Drug Tolerance
Decreased response to constant amounts of the drug.
Functional tolerance: Caused by compensatory changes in receptors, enzymes, or membrane actions of the drug.
Metabolic tolerance: Increased metabolism of the drug, reducing its effects.
Behavioural Tolerance: Ability of the individual to compensate for the drug's effects.
Caffeine Addiction
>500mg a day enough for bad pharmacological effects. Includes muscle tremors, irritability, mental instability.
Withdrawal symptoms includes fatigue, anxiety, headache.
There is a change with the adenosine receptor level associated with dependence. Dependance/withdrawal weak compared to other drugs.
Coffee History
850 AD coffea arabica noticed. 500 AD seeds roasted, and in 800 AD the plant is cultivated and spreads. Reaches Europe mid 17th century, and in NA as well. Arbabian monopoly until the dutch got beans in 1690.
Caffeine in Coffea arabica
As the berries mature and undergo dessication, caffeine goes from 2%-->0.03% dry weight. Caffeine kills some insects, and thats why caffeine is highest in young, soft berries and shoots.
Theobroma cacao
Seeds ground and roasted to make cocao and chocolate drinks. Contains high amount of theobromine
Cola nitida
Important species from the cola plant, which is also high in caffeine. Involved in ceremonies and depresses appetite.
2) Cholinergic Stimulants
Includes nicotiana tabacum and Areca cathechu.
Nicotiana tabacum
Treated scorpion sting, asthma, toothache, cough, etc. by native americans, who used it earlier than the coca plant.
Nicotine
Major alkaloid compound found within the leaves of Nicotiana tabacum. Comes from the alkaloid family pyrrolidine.
Physiological Effects of Nicotine
Has analgesic-like effects: stimulates, depresses, and sedates. Effects focused on the peripheral autonomic nervous system include (causes at low): increased blood pressure and heart rate, neuromuscular blockade (thus muscle relaxant) and nausea. At high causes suffocation and death.
Effects on CNS: Activates dopaminergic reward system, induces anxiety and suppresses appetite.
Pharmacodynamics of Nicotine
Affects both CNS and PNS. Mimics acetylcholine action at nicotinic acetylcholine receptors throughout body. Initially an agonist, before it desensitizes the AchR and becomes an antagonist. May cause epinephrine release from adrenal glands, and norepinephrine and dopamine in the brain.
Nicotine Mechanism
Nicotine competes with acetylcholine to bind with the Nicotinic acetylcholine receptors. Nicotine has many effects because NAChRs are found throughout the body, the the prevalance of Ach at cholinergic synapses is high.
Pharmacokinetics of Nicotine
Smoking tobacco has efficient drug delivery, 90% chance to be absorbed. Lethal dose is 60mg (amount in cigarette is 12mg). Addiction is 7.5-30mg a day (15 cigs). Has fetal affects too.
Addictive Effects of Nicotine
Cravings, depression, mood swings, etc. Postivie reinforcement --> Nicotine intake causes mood elevation and cognitive increases, due to stimulation of dopamine limbic system. Negative reinforcement --> Anxiety reduction
Addiction can be treated with antidepressants, or nicotine replacement.
Carcinogenic/Toxic Compounds in Tobacco Smoke
Carcinogens in cigarette smoke inhibit cancer supressor gene P53, causing cancer, pulmonary and cardiovascular disease. Also causes respiratory problems, as well as problems caused by gases and particulates.
Another Cholinergic Stimulant
Areca catechu nuts are chewed with lime and pepper leaf as 'betel'. Betel acts as a stimulant, contains alkaloids from pyridine, the main one being arecoline. They act as agonists at muscarinic acetylcholine receptors.
Arecoline Mechanism
Muscarinic receptors usually found in smooth muscle, heart, lungs as part of the parasympathetic response. The effects of arecoline include: facial flushing, sweating, increased memory, increased heart rate. Addiction similar to tobacco. Betel has been linked to oral cancer.
3) Adrenergic Stimulants
Includes erythroxylon coca, ephedra sinica, and catha edulis.
Erythroxylon coca
Leaves produce tropane alkaloid called cocaine. Grown in SA cocales. Coca leaf was used for coca cola, vin mariani, depression, etc. Cocaine was isolated 1915, used for local anesthetic.
Cocaine and coca alkaloids
Derived from the aliphatic non-protein amino acid ornithine. Coca alkaloids are known for their tropane ring structure, which can be open or closed.
Extraction of Coca Leaves
Leaves mashed with gasoline (or etw.) to form soluble free base form for alkaloids. Add sulfuric acid for cocaine paste, then converted into water soluble form, cocaine hydrochloride.
Coca alkaloids
Derived from ecgonine: ocaine, cinnamylcocaine and truxilline. Derived from tropine: Tropacocaine, valerine
Derived from hygrine (open ring): Hygroline, cuscohygrine.
Cocaine Effects
Freud (100 years ago): Vivid exhilaration, increased work capacity, elimination for food or sleep.
Stimulates the CNS, gets through blood brain barrier easy. Low doses, dilation of pupils, increased heart rate, bp, temp. Increasing usage: convulsions, respiratory failiure, liver dmg.
The euphora starkly contrasts with the post depression.
Medicinal uses of cocaine
Acts as a vasoconstrictor, and a local anesthetic.Replaced with non-addictive novocaine.
Cocaine mechanism of action
Inhibits the reuptake transporters of dopamine and norepinephrine, resulting in increased levels of neurotransmitters in the synapse.
Catecholamine Biosynthesis
Dopamine: Brain neurotransmitter, that affects limbic pleasure center, as well as stimulates memory and emotions.
Norepinephrine: Stimulates heart and muscle contractions, the more NE, the greater endurance.
Cocaine Addiction
Cocaine associated with reward system, as cocaine prevents dopamine reuptake, which is associated with pleasure. Fatal overdose caused by NE vasoconstriction effect.
Plant Biology of Cocaine
Powerful insecticide. Inhibits function of octopamine, an invertebrate neurotransmitter. NE-like compound not found in mammals.
Chat
Catha edulis. Arabian, twigs chewed. Euphoria, alleviates hunger and fatigue, used for asthma, cough. Side effects include hypertension,agression, etc.
Pharamcology of Chat
Contains cathinone, as well as norpseudoephedrine, and norephedrine, which are natural amphetamines. Enhance the release of catecholamine neurotransmitters through transporters (ephinephrine, norepinephrine). Related to ephedrine in struture/function.
Ephedra major
Middle eastern gnetophyta gymnosperm.
Ephedrine alkaloids
Natural amphetamines. Derived from phenylalanine. Two main alkaloids: ephedrine and pseudoephedrine. Others are norephedrine, pseudonorephedrine.
Historical use of ephedra
Chinese for cough, fever, and to improve circulation. Natives for colds, diuretic, sunburned lips and ointment for sores. Ephedra nevadensis created mormon tea, alternative to tea/coffee.
Modern use of ephedrine
Used for decongestant, like asthma. Sympathomimetic drug. Mimics neurotransmitters that normally activate the sympathetic nervous system. Ephedrine is agonist as alpha A and B adrenergic receptors, where norepinephrine and epinephrine normally bind. This causes bronchial dilation, increases heart rate and blood pressure. Norepinephrine release by sympathetic neurons increased. Also stimulates CNS, counteracts effects of drug induced comas. Also a vasoconstrictor and a heart stimulant. Good for weight loss and stimulant.
Ephedrine as Weight loss
Causes increased heart rate and blood pressure, causing strokes.
Amphetamines
Synthetic ephedrine. Dilate bronchial passages, and stimulate the PNS. Benzedrine, a synthetic, used to clear nasal passages, and for its euphoric effects.
Amphetamine Mechanism
Travels into nerve terminal through uptake, and displaces neurotransmitters from the vesicle into the synapse. Inhibits the intracellular metabolism of neurotransmitters. The flood of NTs in the nerve terminal causes the uptake transporter to reverse, flooding the synapse with NTs. This increases dopamine and norepinephrine levels in the synapse.
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