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Nootropic

Ampakines | Substances of the piracetam group | 5-Hydroxytryptophan

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Nootropics, popularly referred to as "smart drugs," are substances which boost human cognitive abilities (the functions and capacities of the brain). The word nootropic is derived from the Greek words noos or mind and tropein meaning to ward. Typically, nootropics are alleged to work by increasing the brain's supply of neurochemicals (neurotransmitters, enzymes, and hormones), by improving the brain's oxygen supply, or by stimulating nerve growth.

Most alleged nootropic substances are nutrients or plant components (herbs, roots, beans, bark, etc.), available over the counter at health food and grocery stores, and are used as nutritional supplements. Some nootropics are drugs, used to treat retardation, neural degradation (Alzheimer's and Parkinson's), and for cases of oxygen deficit to prevent hypoxia. These drugs have a variety of human enhancement applications as well, are marketed heavily on the World Wide Web, and are used by many people in personal cognitive enhancement regimens.

With some nootropics the effects are subtle and gradual, such as with most nerve growth inducers, and may take weeks or even months before any cognitive improvement is noticed. At the other end of the spectrum are nootropics which have effects that are immediate, profound, and obvious. While scientific studies support some of the claimed benefits it is alleged that certain nootropic substances provide, It is worth noting that many of the claims attributed to a variety of nootropics have not been formally tested. Citations are provided in the article where information is available.

Contents

General strategies

Neurotransmitter support - supplying the body with the precursors and cofactors it needs to produce neurotransmitters. Keeping the brain's neurotransmitters at high levels improves concentration, mental focus, calculation ability, memory encoding, recall, creativity, mood, and cures and prevents most depressions. The four main neurotransmitters are acetylcholine, dopamine, norepinephrine and serotonin.

Note that cardiovascular exercise performed on a regular basis also has nootropic effects, by increasing the body's capacity to supply brain cells with oxygen. Exercise is highly synergistic with nutritional supplementation, and a health regimen is incomplete without it.

Nootropic substances

Nootropic drugs are generally only available by prescription or through personal importation. The other nootropic substances listed below are either nutritional supplements or plant components, and are generally available over the counter at health food and grocery stores. The term "drug" here is used as a legal designation, and does not indicate greater efficacy. With nootropics, the effects, effectiveness, and potency differ from substance to substance and from individual to individual. See the substance descriptions below for more detail.

Replenishing and increasing neurotransmitters

Thinking is a biologically demanding task. It involves the firing of neurons which requires plenty of neurotransmitters, and even though these are reuseable to some extent, they do get depleted. Depletion of neurotransmitters generally results in reduced mental performance, which may include difficulty concentrating, slowed reasoning, decreased learning efficiency, impaired recall, reduced coordination, lowered moods, inability to cope, increased response times, and mental fatigue. This also generally increases the likelihood of human error on tasks and activities performed. Stress causes neurotransmitters to be depleted even faster. The brain's neurotransmitters need to be replenished frequently, made by the body from substances ingested in the diet. Maintaining neurochemicals at optimal levels has a corresponding effect on brain performance, supporting improved mental agility and stamina, even beyond the individual's normal limits.

As the brain ages, its ability to produce and maintain youthful levels of neurotransmitters declines.[1] Thus, the theory is that by providing the brain with ample raw materials to make the neurotransmitters it needs can restore them to more youthful levels to help maintain cognitive function at vigorous youthful levels as well.

Cholinergics

Cholinergics are substances which affect the neurotransmitter acetylcholine or the components of the nervous system which utilize acetylcholine. Acetylcholine facilitates memory, concentration, focus, and high-order thought processes (abstract thought, calculation, innovation, etc.). Increasing the availability of this neurotransmitter in the brain may improve these functions and increase the duration in which they may be engaged without slowing down or stopping. Oversupplying the brain with acetylcholine may have the opposite effect, temporarily reducing rather than improving mental performance. Cholinergic nootropics include acetylcholine precursors and cofactors, and acetylcholinesterase inhibitors:

  • Acetyl-L-carnitine (ALCAR) - Amino acid. Precursor of acetylcholine (donating the acetyl portion to the acetylcholine molecule). It is synergistic with lipoic acid.
  • Centrophenoxine (Lucidril) - Drug. cholinergic agent, enhances color perception.
  • Choline - precursor to acetylcholine (an essential component of the acetylcholine molecule).
    • Alpha-GPC (L-alpha glycerylphosphorylcholine, Choline alfoscerate) - most effective choline precursor, readily crosses the blood-brain barrier.
    • CDP-Choline (Cytidine Diphosphate Choline) - choline precursor, tends to be less expensive and similar in effect to Alpha GPC.
    • Choline bitartrate - precursor of acetylcholine, general nootropic, anti-depressant.
    • Choline citrate - precursor of the neurotransmitter acetylcholine, general nootropic, anti-depressant.
  • DMAE - approved treatment for ADD/ADHD, precursor of acetylcholine, cholinergic agent, removes lipofuscin from the brain, anti-depressant.
  • L-Huperzine A - potent acetylcholinesterase inhibitor derived from Chinese club-moss.
  • Lecithin - precursor of acetylcholine.
  • Pyrrolidone derivatives:
    • Piracetam (Nootropil) - Prescription drug (in Europe). The original (first)[2], and most commonly taken[3] nootropic drug. It is a cholinergic agent, synergistic with DMAE, centrophenoxine, choline, and Hydergine. Increases brain cell metabolism and energy levels[4], and speeds up interhemispheric flow of information (left-right brain hemisphere communication). Increases vigilance,[5], improves concentration, and enhances memory. Protects neurons from hypoxia,[2] and stimulates growth of acetylcholine receptors. May also cause nerves to regenerate. Piracetam markedly decreases the formation of neuronal lipofuscin.[6] It improves posture in elderly people.[7] It is not regulated in the US.
    • Aniracetam - Drug. Analog of piracetam, and 4 to 8 times more potent. Like piracetam, aniracetam protects against some memory impairing chemicals, such as diethyldithiocarbamate and clonidine.[8] Also like piracetam, aniracetam may enhance memory in aging adults by increasing levels of brain biogenic monoamines, which are beneficial to learning and memory.[1] Both racetams have possible therapeutic use in treating fetal alcohol syndrome.[9] Aniracetam increases vigilance.[5]
    • Etiracetam - It increases vigilance.[5]
    • Nefiracetam - Drug. Analog of piracetam, and facilitates hippocampal neurotransmission.[10]
    • Oxiracetam - Drug. Analog of piracetam, and 2 to 4 times stronger. Improves memory, concentration, and vigilance. When fed to pregnant rats, the offspring of those rats were more intelligent than the offspring of rats fed a saline solution placebo.
    • Pramiracetam - Drug. Fifteen times stronger than piracetam, of which it is an analog.
  • Vitamin B5 - cofactor in the conversion of choline into the neurotransmitter acetylcholine, cholinergic agent, increases stamina (including mental stamina).

CAUTION: Excess acetylcholine can be potentially harmful; see cholinesterase inhibitor.

Dopaminergics

Dopaminergics are substances which affect the neurotransmitter dopamine or the components of the nervous system which utilize dopamine. Dopamine is produced in the synthesis of all catecholamine neurotransmitters, and is the rate limiting step for this synthesis. Dopaminergic nootropics include dopamine precursors and cofactors, and dopamine reuptake inhibitors:

  • L-dopa - Prescription drug. Precursor to the neurotransmitter dopamine, general nootropic, anti-depressant.
  • Phenylalanine (requires Vitamin B6 and Vitamin C) - Essential amino acid. Precursor to dopamine, general nootropic, anti-depressant, sleep reducer.
  • Theanine - Found in tea. Increases serotonin and dopamine levels in the brain. Increases alpha-wave based alert relaxation.
  • Tyrosine (requires Vitamin B6 and Vitamin C) - Amino acid. Precursor to dopamine, general nootropic, anti-depressant, sleep reducer.
  • Vitamin C- improves cardiovascular elasticity and integrity, membrane stabilizer and major anti-oxidant (protects brain cells and prevents brain cell death), cofactor in the production of the neurotransmitters dopamine and serotonin.
  • Vitamin B6 - co-factor used by the body to produce dopamine.
  • Yohimbe - Bark. Boosts dopamine levels as much as 80%, though how it does this is not yet understood. Aphrodesiac. Yohimbe poses some health risks through its side-effects: it is a neuro-paralytic which slows down breathing and induces acidosis, some symptoms of which are malaise, nausea, and vomiting. Contraindicated for users of megadoses of acidic vitamins or nutrients.

Deprenyl - Blocks MAO B (the neuroenzyme that breaks down dopamine) thus raising Dopamine better and faster than other drugs.

Serotonergics

Serotonergics are substances which affect the neurotransmitter serotonin or the components of the nervous system which utilize serotonin. Serotonergic nootropics include serotonin precursors and cofactors, and serotonin reuptake inhibitors:

  • 5-HTP - more bioavailable form of tryptophan, precursor to the neurotransmitter serotonin, promotes relaxed poise and sound sleep.
  • Griffonia simplicifolia a natural source of 5-HTP (an alternative in countries where 5-HTP not legal, freely available.)
  • Theanine - Found in tea. Increases GABA and dopamine levels in the brain. Increases alpha-wave based alert relaxation.
  • Tryptophan (requires Vitamin B6 and Vitamin C) - Essential amino acid. Precursor to serotonin, found in high concentration in bananas and poultry (especially turkey), also in milk, promotes relaxed poise and sound sleep.

Anti-depression, adaptogenic and mood stabilization

Depression and depressed mood negatively affect cognitive performance. Feelings of sadness, guilt, helplessness, hopelessness, anxiety, and fear caused by depression detract from productive thought, while apathy (which is also induced by depression) is the lack of motivation and driving moods (like curiosity, interest, determination, etc.) Other symptoms include disturbed sleep patterns, mental fatigue and loss of energy, trouble concentrating or making decisions, and a generalized slowing and obtunding of cognition, including memory. Obviously, removing these effects improves intelligence and mental performance, and therefore, counteracting and preventing depression are effective nootropic strategies. There is a high correlation between depression and a reduction or depletion of neurotransmitters (dopamine, acetylcholine, and serotonin) in the brain, therefore it is no surprise that increasing the brain's supply of neurotransmitters alleviates (or at least reduces the symptoms of) most depressions. Stress is another major factor in neurotransmitter depletion, being both a cause and effect of it (creating a vicious downward cycle), therefore stress management and anti-stress substances are also very useful nootropic strategies.

All of the "nergics" listed above have been found to increase stress tolerance and alleviate depression (by replenishing or increasing the brain's supply of specific neurotransmitters), especially when used in precursor/co-factor combinations.

Here are some more nootropics which affect mood and stress:

  • Ashwagandha (Withania somnifera) - Root. Also known as Indian ginseng. Adaptogen used as a tonic to normalize body processes and reduce stress and anxiety.
  • Inositol - Is a B-vitamin like substance with anti-anxiety effects. It is believed to produce its anti-anxiety effects by improving the binding of gabaergics to GABAA receptors. Inositol is a sugar, and is therefore an alternative energy source for brain and muscle tissues. It produces a sugar high without a sugar low, making it especially suited for sweetening tea (instead of sugar). It is also a membrane stabilizer which can strengthen (and therefore help protect) neurons.
  • Lemon Balm (Melissa Officinalis) - Herb. Anti-depressant.
  • Rhodiola Rosea - Herb. Adaptogen; elevates mood, alleviates depression. Promotes mental energy and stamina, reduces fatigue.
  • St John's Wort - Herb. The active components: hypericin and hyperforin, are clinically indicated to be effective in cases of mild to medium depression.
  • Ginseng, Siberian (Eleutherococcus senticosus) - Root. Anti-anxiety adaptogen that normalizes physical stress and mental consequences.
  • Selegiline (Deprenyl) - Along with Piracetam and Meclofenoxate, Deprenyl decreases the amount of lipofuscin pigment and ceroid pigment accumulations in the brain by improving cellular recycling activities.[11] Therefore, these nootropics may slow age related diseases in the brain.
  • Sutherlandia Frutescens - Herb. Adaptogen, blood detoxifier.
  • Tea - Herb. Contains theophylline and theanine. Increases alpha-wave based alert relaxation (relieves stress).
  • Theanine - Amino acid. Found in tea. Increases serotonin and dopamine levels in the brain. Increases alpha-wave based alert relaxation.
  • Vasopressin - Drug. Memory hormone produced by the pituitary gland which improves both memory encoding and recall. Rapidly counters chronic apathy syndrome and drug-induced vasopressin depletion.
  • Nicotinic acid (vitamin B3) - Essential nutrient. Mild enhancer of concentration and memory. Vasodilator. Mood stabilizer, with a powerful anti-anxiety effect — perhaps the best and most immediate stress reliever available (note that other forms of vitamin B3 do not have this effect). Side effects: gastric upset (which is easily prevented and relieved with antacids), reduced blood pressure and flushing of the skin (caused by vasodilation), and itchy sensation in the skin caused by histamine release.

Brain energy and improved oxygen supply

  • Acetyl-L-carnitine (ALCAR) - Amino acid. Transports fatty acids through cellular membranes and cytosol into cells' mitochondria, where the fats undergo oxidation to produce ATP, the universal energy molecule. Synergistic with lipoic acid.
  • Chromium- stabilises blood sugar levels promoting concentration.
  • Coenzyme q-10 syn. Ubiquinone - increases oxygen transport through the mitochondria of the cells. Appears to slow age-related dementia.
  • Creatine - increases brain energy levels via ATP production.
  • Inositol -
  • Lipoic acid - synergistic with Acetyl-L-carnitine.
  • Pyritinol (Enerbol) - Drug. Enhances oxygen and glucose uptake in the brain, and allows glucose to pass more easily through the blood-brain barrier. Improves general brain function. It is also a powerful anti-oxidant which scavenges hydroxyl radicals created in the very processes it is involved in.
  • Vinpocetine - micro-circulation enhancer, improves oxygen supply to brain cells.

Mental agility, concentration, stamina, and focus

  • Adrafinil (Olmifon) - Drug.
  • Caffeine - improves concentration, idea production, but hinders memory encoding. Also produces the jitters. Caffeine is the most widely used psychoactive substance in the world.
  • Coffee - Bean. Contains caffeine; brewed coffee is high in antioxidants.
  • Nicergoline - Drug. Nicergoline is an ergoloid mesylate derivative used to treat senile dementia. It has also been found to increase mental agility and enhance clarity and perception. It increases vigilance.[5] Increases arterial flow and use of oxygen and glucose in the brain.
  • Nicotine - stimulus barrier (aids in concentration). Stimulus barrier rebound effect (an unpleasant side effect).
  • Cocaine - Drug
  • Phenibut -
  • Theophylline -

Memory enhancement and learning improvement

All of the "nergics" listed above improve memory (encoding and recall). So do all nootropics which improve general brain performance such as the brain energy and oxygen suppliers listed above, and the nerve growth stimulants and protectants listed in their own section below. Other nootropics with specific effects on memory encoding and recall include:

  • Bacopa monniera Linn. (Brahmi) - Herb. Elevates curiosity, enhances memory and concentration.[12] Brahmi also protects against amnesia inducing chemicals such as scopolamine or loss of memory due to electro convulsive shocks.[12] It is a traditional ayurvedic medicine.
  • Rosemary - Herb. Rosemary has a very old, albeit unverified reputation for improving memory.
  • Vasopressin - Hormone, prescription drug.

Nerve growth stimulation and brain cell protection

  • Acetyl-L-carnitine (ALCAR) - Amino acid. Inhibits lipofuscin formation.
  • Bacopa monnieri (Brahmi) - Herb. Improves protein synthesis in brain cell repair and new dendritic growth.
  • Selegiline (Deprenyl) - Drug. Brain cell protectant, delays senescence of brain cells, proven to increase maximum life span in laboratory rats.
  • Ergoloid mesylates (Hydergine) - Drug. Mimics nerve growth factor (NGF), and is a powerful anti-oxidant capable of delaying brain death in cases of heart failure and stroke by several minutes with regular use. It increases vigilance.[5]
  • Idebenone - stimulates nerve growth, and has same effects as Coenzyme q-10 without its harmful side-effects.
  • Inositol - Membrane stabilizer. Strengthens neurons, making them less susceptible to damage.
  • Pyritinol (Enerbol) - Drug. Powerful anti-oxidant which scavenges hydroxyl radicals. Also enhances oxygen and glucose uptake in the brain, and allows glucose to pass more easily through the blood-brain barrier. Improves general brain function.
  • Rasagiline (Azilect) - Drug. Treats Parkinson’s disease either as monotherapy (by itself) or in addition to levodopa therapy. Promotes increased and sustained levels of dopamine by selectively inhibiting an enzyme, monoamine oxidase-B.
  • Vitamin C - Membrane stabilizer, involved in collagen synthesis. Strengthens neurons, making them less susceptible to damage. Vitamin C is also a co-factor in the brain's production of dopamine, and therefore it also has general nootropic effects.

Sleep enhancement or reduction

  • Vitamin B12 - Can greatly enhance the color of dreams. Stimulates brain neuron RNA synthesis.

Recreational drugs with purported nootropic effects

  • Amphetamines (Adderall, Dexedrine) - Schedule II / Class B drugs. Prescribed for attention-deficit disorders, narcolepsy, and certain cases of obesity; and issued as an anti-fatigue pill for pilots in the armed forces. These also heighten alertness, mental focus, vigilance, stamina, and sex drive. They are highly addictive, and have many side effects. Personal importation is prohibitted. Using these recreationally or for performance enhancement is illegal in most countries.
  • LSD - Schedule I / Class A drug. At minuscule doses (1 mcg) the drug has effects similar to Hydergine. Overdose and side-effects: produces inebriating hallucinogenic and entheogenic effects at doses as low as 20–30 μg (micrograms), with the likelihood of having a bad trip increasing as dose is increased if these effects are undesired. May also cause cognitive shifts, synesthesia, and flashbacks. The drug sometimes spurs long-term or even permanent changes in a user's personality and life perspective. 
  • 4-methylaminorex
  • Pemoline
  • Psilocybin
  • Psilocin

Other nootropics

  • Adafenoxate - Has an anti-anxiety effect for rats[13] and possibly the same for humans.
    Butea frondosa - "The plant Butea frondosa has been indicated in the Indian system of medicine as a plant augmenting memory and as a rejuvenator. ... B. frondosa possesses antistress and weak nootropic activity."[14]
    BMY 21502 - Injured animals treated with BMY-21502 at one week post-injury showed significant improvement in post-injury learning ability compared to injured animals treated with vehicle. Paradoxically, in uninjured control animals BMY-21502 treatment appeared to worsen learning scores. The results of this study indicate that BMY-21502 may be useful for attenuating the dysfunction in learning ability that occurs following TBI.
    Cabergoline (Dostinex) -
    Celastrus Panicaltus - Herb.
    Cerebrolysin - A neuroprotective nootropic agent, might affect Alzheimer's disease pathology. Currently in clinical trials
    Coluracetam - It may also have potential use in prevention and treatment of ischemic retinopathy and retinal and optic nerve injury.
    Desmopressin (DDAVP) - Drug. Analog of vasopressin (the anti-diuretic and memory hormone)
    DHEA -
    Dostinex -
    Fasoracetam -
    Essential Fatty Acids- EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are the best known. EPA in particular, has an anti-depressant function and is positively indicated in trials with autism and learning difficulties.
    Fipexide (Vigilor) - It protects against some memory impairing chemicals, such as diethyldithiocarbamate and clonidine.[8]
    Gabapentin (Neurontin) - Anticonvulsant with nootropic effects
    Galantamine - Drug.
    Gerovital H3 -
    Ginkgo biloba - Root. Increases blood flow to the extremities including the brain, nootropic effects are disputed.
    Gotu Kola - Herb and root.
    Meclofenoxate - Has an anti-anxiety effect for rats[13] and possibly the same for humans. Like Fipexide, it protects against some memory impairing chemicals, such as diethyldithiocarbamate and clonidine.[8] Like many racetams, it may treat fetal alcohol syndrome.[9]
    Milacemide - Drug.
    Nimodipine -
    Ondansetron -
    Oxiracetam (Neuromet) -
    Phenytoin (Dilantin) -
    Phosphatidylserine- reduces age-related memory loss and promotes concentration.
    Picamilon - Drug.
    Pikamilone -
    Pregnenolone -
    Propranolol (Inderal) - Drug. Flight response inhibitor, treats phobias, anti-anxiety effect. Though it has a host of negative side effects including but not limited to diabetes complications, depression, and impotence.
    Pyroglutamate -
    Semax - A neuropeptide (stimulator of the nervous system) developed from a short fragment of ACTH, Pro8-Gly9-Pro10 ACTH(4-10). Claims of significant increase in salvation of neurons are made
    Somatotropin -
    Sulbutiamine (Arcalion) - Drug.
    Xanthinol -

Related pages

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External links

Notes

  1. ^ a b Stancheva et al. 1991
  2. ^ a b McDaniel et al. 2002
  3. ^ Goldman et al., 1999 cited in McDaniel et al. 2002
  4. ^ Gabryel & Trzeciak 1994 cited in McDaniel et al. 2002
  5. ^ a b c d e Saletu & Grunberger 1985
  6. ^ Paula-Barbosa et al. 1991
  7. ^ Riedel et al.
  8. ^ a b c Genkova-Papasova & Lazarova-Bakurova 1988
  9. ^ a b Vaglenova & Petkov 2001
  10. ^ Nomura & Nishizaki 2000
  11. ^ Riga & Riga 1995
  12. ^ a b Singh & Dhawan 1997
  13. ^ a b Petkov et al. 1987
  14. ^ Soman et al. 2004

References

Books

  • The Edge Effect. Reverse or prevent Alzheimer's, aging, memory loss, weight gain, sexual dysfunction and more. By Eric R Braverman MD. Excellent book describing the four primary neurotransmitters, the role they play in mental and physical functioning, and how to increase levels in the brain. ISBN-10: 1-4027-2247-8. ISBN-13: 978-1-4027-2247-9.
  • Brain Boosters. Foods And Drugs That Make You Smarter. (A quote from the book: "It's hard to distinguish between the health and anti-aging uses of the smart drugs and nutrients.") By Beverly Potter & Sebastian Orfali. Ronin Publishing. 1993. Paperback, 257 pages. ISBN 0-914171-65-8
  • Brain Fitness. Anti-Aging Strategies To Fight Alzheimer's Disease, Supercharge Your Memory, Sharpen Your Intelligence, De-Stress Your Mind, Control Mood Swings, and Much More... By Robert Goldman, M.D, D.O., Ph.D., With Ronald Klatz, M.D., D.O., and Liza Berger. Doubleday. 1995. Paperpack, 346pp. ISBN 038588696
  • Brain Longevity: The Breakthrough Medical Program that Improves Your Mind and Memory. By Dharma Singh Khalsa.
  • Life Extension. A Practical Scientific Approach. Adding Years to Your Life and Life to Your Years. Part III, Chapter 4: Revitalizing Your Brainpower. By Durk Pearson and Sandy Shaw. Warner Books. 1982. Hardcover, 858pp. ISBN 0-446-51229-X
  • Mind Boosters: A Guide to Natural Supplements that Enhance Your Mind, Memory, and Mood. By Ray Sahelian. St. Martin's Griffin; 2000. Paperback, 300 pages. ISBN 0-312-19584-2
  • Mind Food and Smart Pills. How To Increase Your Intelligence and Prevent Brain Aging. By Ross Pelton. 1986. Paperback, 170pp. ISBN 0-936809-00-0
  • Smart Drugs & Nutrients. How To Improve Your Membory And Increase Your Intelligence Using The Latest Discoveries In Neuroscience. (Many of the substances in this book have life-extending or cell regenerating effects.) By Ward Dean, M.D. and Joh Morgenthaler. B&J Publications. 1990. Paperback, 222pp. ISBN 096271892
  • Smart Drugs II: The Next Generation : New Drugs and Nutrients to Improve Your Memory and Increase Your Intelligence. By Ward Dean (M.D.), John Morgenthaler, Steven Wm Fowkes. Smart Publications. 1993. Paperback, 287 pages. ISBN 0-9627418-7-6
  • Your Personal Life-Extension Program. A Practical Guide to the New Science That Can Make You Stronger, Smarter, Sexier, More Energetic, and More Youthful. Chapter 14: Therapies to Improve Memory and Intelligence. By Saul Kent. Morrow. 1985. Hardcover, 384 pages. ISBN 0-688-00629-9

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