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1. NT - receptor interaction.











2. ephedrine








3. Noradrenergic receptor

4. NE release




5. Bodybuilder

6. Steroid Hormone Response

7. Erythropoietin

8. Epogen

9. Racing

 

HOW PERFORMANCE ENHANCERS WORK

A BRIEF LESSON ABOUT DRUG TARGETS
All drugs have their own ‘mechanism of action’ – or way in which they work. Most drugs' act at specific target called receptors. These specialized proteins are located on cell membranes or inside cells in your body. To visualize this concept, picture an outlet, like the one on a wall. Now picture several of these outlets – or receptors – on the cells in your body. These receptors act as switches that can either trigger or block biological activity when stimulated/occupied. Drugs, and natural chemicals in the body occupy, bind, or plug into the outlets to cause varying effects.

An example of a receptor – the adrenergic receptor – is shown to the left in Figure 1. The endogenous or natural chemical, norepinephrine, binds to its receptor on a cell membrane, triggering a series of biochemical reactions and cellular “work”. Throughout this presentation, you will hear about each drug’s mechanism of action, and the receptors with which it interacts.

An agonist is a drug or other chemical that can bind to a receptor to produce a physiologic reaction typical of a naturally occurring substance. Ephedrine can act as an agonist of norepinephrine at adrenergic receptors.

An antagonist is chemical substance or drug that interferes with the physiological action of another, especially by binding and blocking its receptor.

STIMULANTS (EPHEDRINE AS EXAMPLE)
Stimulants are used generally by athletes to stay alert, reduce fatigue, and maintain aggressiveness. These drugs make the heart beat faster, open up lung passages to make breathing easier, and help the brain focus better.

Ephedrine, is the active compound in the plant called Ephedra or Ma Huang. It is an alkaloid because it contains a nitrogen atom (see blue atom in Figure 2). A less potent version of ephedrine found in the Ephedra plant is pseudoephedrine, which is contained in many popular decongestant cold remedies. Ephedrine is banned from the competitive arena by the IOC, the IAAF, the USOC, the NCAA.

For more information about alkaloids found in plants go to www.thepepproject.net and click on Module 5.

HOW DOES EPHEDRINE WORK?
Ephedrine acts at the norepinephrine synapse, the connection between a neuron that releases norepinephrine and a neighboring cell.

Norepinephrine is stored in vesicles in the terminal of a neuron (shown in Figure 3). Normally norepinephrine (also called noradrenaline) is released in small quantities from the vesicles into the synaptic space. Then it binds to adrenergic receptors on the receiving cell, and depending on what type of receiving cell is present, e.g., a neuron or a cardiac cell, a specific response is produced. Neurons might fire, or a cardiac cell might fire to increase the heart rate.

Ephedrine’s principal mechanism of action, like that of amphetamine, is to cause more norepinephrine to be released from its storage vesicles in the terminal of neurons (Figure 4). This increases the amount of norepineprhine in the synaptic space compared to normal conditions. More norepinephrine binds to adrenergic receptors, resulting in relaxation of the bronchioles, increased heart rate and blood pressure, and a generally increased state of arousal. These effects are sometimes called an “adrenaline rush”. Ephedrine can also bind to adrenergic receptors to mimic the actions of norepinephrine.

WHAT ARE STEROIDS?
Steroids are hormones or chemical substances derived from cholesterol. The human body produces several kinds of steroid hormones. Of the ‘sex steroids’, males produce mainly testosterone. Females produce mainly estrogen and progesterone.

ANABOLIC/ANDROGENIC STEROIDS
Testoterone has both anabolic and androgenic effects. The ability of testosterone to stimulate muscle and bone and cells to make more protein is called the anabolic effect. The ability of testosterone to enhance male reproductive and secondary sex characteristics (testicle development, hair growth, deepening of the voice) is called the androgenic effect.

Anabolic steroids are synthetic analogs of testosterone. All anabolic steroids have some degree of androgenic effects.

HOW DO ANABOLIC STEROIDS WORK?
Like natural steroids, these synthetic steroids bind to steroid receptors in many kinds of cells (see Figure 6). The steroid and its receptor are then carried to the nucleus where they ‘instruct’ the DNA to transcribe messenger RNA (mRNA). The mRNA then delivers its message to the ribosomes in the cytoplasm causing a an increase protein synthesis. In muscle cells, this causes muscle growth. In bone cells, this increases bone size.

To learn more about how steroids work, go to www.thepepproject.net and click on Module 6.

NATURAL BLOOD BOOSTERS: EPO
Erythropoietin, or EPO, is a naturally occurring hormone produced in the kidneys. Specific “sensors” in the kidneys monitor the oxygen (O2) content in the blood (arterial side). If the amount of oxygen drops below a certain level, EPO is released into the bloodstream. It then binds to specific EPO receptors on the surface of cells in the bone marrow resulting in the production of more erythrocytes (red blood cells). An increased number of red blood cells carries an increased amount of oxygen to all cells in the body.

SYNTHETIC BLOOD BOOSTERS — EPOGEN®
Epogen® (Epoetin alfa) is a genetically engineered version of the natural hormone erythropoietin (EPO) found in the body. This synthetic version of EPO is used to treat anemia associated diseases such as diabetes and kidney disease. However, athletes use synthetic EPO to enhance their performance.

Epogen works the same way as natural EPO. When administered intravenously, it travels to the bone marrow where it interacts with EPO receptors to stimulate the production of red blood cells from bone marrow stem cells. The increase in the number of red blood cells delivers more oxygen to all cells in the body, especially muscle cells.

WHY DO ATHLETES TAKE EPO?
Athletes get an extra edge if they are able to get more oxygen to their muscles. By taking synthetic EPO, athletes can boost their red blood cell count and are able to supply their muscles with oxygen for a longer amount of time. Imagine oxygen as the fuel necessary to make the muscles work most effectively--EPO essentially gives the athlete more fuel for their muscles. This leads to increased performance and an unfair advantage over competitors.

Endurance athletes who use EPO can increase their the oxygen carrying capacity of their red blood cells by as much as 7 to 10 percent!



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