Stimulants

Stimulants are substances that manifest their effects in the organism by affecting on central nervous system(CNS), activating adrenergic system. The catecholamines   dopamine,   L(-)-epinephrine   and  L(-)-norepinephrine act in the body as neurotransmitters   as well as as hormones. Norepinephrine is the predominant neurotransmitter, whereas epinephrine the major hormone. Catecholamines are released from the nervous system following neuronal depolarization. The ratio of L(-)-epinephrine  and L(-)-norepinephrine is about 80:20 in humans.

Following stimulants effects manifest also through somatic functions through mediators of sympatic nervous system – catecholamines(dopamine, adrenaline and noradrenaline).

Dopamine

Epinephrine

Norepinephrine

The most significant deputes from this group are:

• Ephedrine and analogs,
• Amphetamine and analogs,
• Cocainics and others.

Physiology of adrenergic nervous system, adrenergic medicaments

Adrenergic medicaments(simpaticomimetics) cause similar or identic effects as adrenergic nerves stimulation. Action is done directly through connection of these substances to adrenergic receptors in tissues or indirectly, by releasing of catecholamines from adrenergic nerves.

Substances with adrenergic effect are divided into four groups:

1)      Catecholamines: noradrenaline, adrenaline and dopamine

2)      Adrenergic vasoconstrictors: ephedrine, phenylephrine, metoxamine, metaraminol, naphazoline…

3)      Adrenergic bronchodilators: isoprenaline, orcirenaline, salbutalin, terbutaline…

4)      Adrenergic stimulanses of CNS: amphetamine, metamphetamine...

Noradrenaline, adrenaline and dopamine are the most significant represents from the group of catecholamines. Effects of these substances are exerted through adrenergic alpha and beta receptors, while effects of dopamine are mostly exerted through dopaminergic receptors.

Alpha receptors stimulation leads to: vasoconstriction, mydriasis(pupils dilatation), smooth digestive tract muscles relaxation. The most important of beta-adrenergic receptors stimulation are: frequency, contractability and heart irritability increase( increase in heart minute volume), bronchodilatation and vasodilatation.

Some synthetic medicaments affect primarily over alpha, and others over stimulation of beta receptors. Beta-1 receptors are located primarily in heart, and beta-2 receptors are most widespread in the muscle of bronchials. There is a differentiation among adrenergic substances related to affinity according to beta-1 and beta-2 receptors.

Adrenergic beta-receptor is localized on outer surface of cell membrane in effector organs.

Beta receptor is by chemical composition enzyme adenyl cyclase, that influents on the increase of cyclic adenosine-monophosphate(cAMP) through stimulation. Through activation of protein kinase cAMP starts the processes from which depend functions of effectory organs. Beta-2 receptors are primarily located in bronchials( beta-2 receptors are present in miocard,too). Activation of these receptors causes bronchodilatation(relaxation of bronchial muscles), which is therapic effect at asthmatic patients.

Among other effects, catecholamines cause increasing of glycogenolysis and lypolisis. The result of these effects is increase in glucose concentration(liver) and free fatty acids in blood, just as the increase in lactic acid concentration in muscle fibers. Catecholamines, and especially adrenaline, increase calorygenesis, which is followed by increased production of oxygen. Increased level of potassium in plasma is the following phenomenon of catecholamine effect.  

Appliance in sport

Affecting stimulatively on central nervous system, these substances excite, make mental processes faster and more efficient, contain hunger and thirst. Psychostimulants remove pain during the fight or match. Psychostimulants also make physical activity easier and increase the time needed for fatique creation. Knowing that fatique created by physical work asks for intensity decrease or training stop, abuse of the stimulants leads the organism in the condition of danger, when various damages can be created.

Increase in muscle contractility and acceleration in muscular reaction are the reasons for use of these substances in sport. Inhibitory effect of stimulanses on appetite and increased calorygenesis, that should lead to body mass reduction(fat) are the reasons for the usage in recreational sports.

Harmful effects

Stimulants abuse leads to following dangers:

• Possibility of collapse and lethal outcome(death)
• Increase of blood pressure
• Heart rhythm disorders(risk from the damage of the heart)
• Dehydration and hyperthermia or heatstroke(can be fatal)
• Possibility of dependence disease
• Aggressivity and fear.

Detection

Stimulants can be detected in urine by appliance GH-MS, and in some cases by application of high resolution MS.

Cathine concentration in urine that is bigger than 5µg/ml is taken for illegal.

Ephedrine and methylephedrine concentration that is bigger than 10µg/ml is taken for illegal.

Ephedrine

Ephedrine is the representor of the vasoconstrictors group(phenilephrine, metoxamin, metaraminol and naphazoline). Therapeutic application of these substances means causing of local(decrease in swelling of the nasal mucosa) and general vasoconstriction.

Ephedrine is primarily isolated from Chinese plant Ma Huang(Ephedra vulgaris).

Ephedra vulgaris

Mostly, ephedrine effects by releasing catecholamines, and less directly on adrenergic receptors. Ephedrine effects are different from catecholamines by following:

• Last a lot longer
• Perform even after oral application
• At repeated application tachyflaxia appears(tachyflaxia represents acute shape of tolerance. This appearance is seen already after few doses of medicine. In the case of ephedrine, this appearance is explained by exhaustion of catecholamines reserves in the endings of adrenergic nerves)
• Effects are manifested on CNS, too.

The most important effects after oral appliance are:

• Vasoconstriction and blood pressure increase
• Bronchodilatation
• Mydriasis(pupil dilatation)
• CNS stimulation
• Increased skeletal muscles contractility
• Increased glycogenolysis and lypolisis.

Last years ephedrine is found in combined rimifons that are specialized for fat reduction in organism.

The most important harmful effects are:

• Tachycardia
• Urine retention
• Nervousness and insomnia

Amphetamine

In the history of amphetamine use as a doping the appearance of “fast doping” use is also seen in 70s and 80s of the last century. In this period there were even 20 death cases caused by abuse of amphetamine.

Amphetamine affects stimulatively on central nervous system by increasing psychomotor abilities and stimulating medullar centers. This substance also manifests adrenergic effects on peripheria.

Psychological effects of applied amphetamine are:

• Fatique decrease(athletes have less problems to handle hard trainings and pay less attention to injuries)
• Increase of initiation and mood(athletes feel themselves stronger, more energized and faster)

These effects are applied 10-30 minutes after amphetamine intake.

Peripheral amphetamine effects are:

• Vasoconstriction and arterial pressure increase
• Increase of heart frequency
• Bronchial dilatation
• Pupils dilation(mydriasis).

Metabolic amphetamine effects are:

• Increase in oxygen consumption and basal metabolism values
• Increase of free fat acid concentration in blood.

Harmful effects

Harmful effects occur when amount that is 10-20 times bigger from therapeutic is intaked(therapeutic is 5-25mg). Poisoning can occur even at 30mg per day. Hard cases of poisoning are followed by convulsions, coma and lethal outcome. There were cases of athletes that survived extreme doses of 400-500mg per day.

The most important harmful effects are:

• Insomnia(inability to sleep)
• Heavy motor restlessness
• Hallucinations
• Suicidal and homicidal tendencies
• Harmful effects to cardiovascular system: palpitations, arrhythmia, anginal pain, hyper-pirexia and headache
• Development of drug
• Loss of apettite(weight loss).

Rimifon is intaked parentally(intramuscular), cause effect is unstabile during oral use.

Amphetamine can be found after half an hour from the moment of intake in urine, and it is possible to be detected 2-3 days after intake. Differences in time of appearance and the amount of excreted metabolits vary of dose intaked.

Parental usage is more practical, cause rimifon is unstable during oral usage.

Cocaine

Cocaine is the alkaloid from the plant Erythroxylon coca, originating from South America.

 Erythroxylon coca

Cocaine effects

Central nervous system

It is thought that cocaine, in some areas of the brain, increases releasing(concentration) of neurotransmitters: dopamine, epinephrine and norepinephrine that are natural activators of CNS. Effects of these transmitters are increased by the block of its reabsorption in the ends of its neural endings. Middle part of the brain, in which centers for emotional event are located, specially react to intaked cocaine.

Manifests of cocaine effect are:

• Euphoria followed by laugh, restlessness and hilarity
• Impulsive behaviour, enterprise, self confidence, talkativeness, sexual disinhibition.

On this phase supervenes the phase of illusory phenomena and hallucinations.

After increase, it comes to decrease of neurotransmitters concentration, which is followed by symptoms of depression, lethargy and sadness.

Cocaine is thought to be an aphrodisiac, but repeated long-term use leads to impotence.

Cocaine leads to development of all drug addiction phenomena(tolerance and apstinential crisis).

Cardiovascular system

Cocaine increases heart rate frequency and blood pressure. This effect is sudden and strong.

Cocaine can be intaked in following ways:

• Parental(injections)
• Smoking – crack
• Sniffing into the nose

After parental use effect on brain is seen after 15 seconds, while smoking shows effects after 10 seconds. Effects of this drugs vanish after an hour, and it gives a great incentive for repeated and more often use.

Appliance in sport

Fatique removal, euphoria, self confidence increase, working motivation increase, competitiveness, pain removal are the basic motives for cocaine use in sports.

Harmful effects

The spectar of harmful effects is huge. Signs of cocaine intoxication are: tachycardia, chest pain, arrhythmia, vomiting, dizzy, dyspnea(feeling of harder breathing), fears, confusion and convulsions. Lethal outcomes are seen, too.

This is the list of prohibited stimulants, including their D- and L- isomers:

Adrafinil, amfepramone, amiphenazole, amphetamine, amphetaminil, benzphentamine, bromantan, carphedon, cathine, clobenzorex, cocaine, dimethylamphetamine, ephedrine, etilamphetamine, etilephedrine, fencamfamin, fenetylline, fenfluramine, fenproporex, furfenorex, mefenorex, mephentermine, mesocarb, metamphetamine, methylamphetamine, methylenedioxyamphetamine, methylenedioxymethamphetamine, methylephedrine, methylephedrine, methylphenidate, modafinil, nikethamide, norfenfluramine, parahydroxyamphetamine, pemoline, phendimetrazine, phenmetrazine, phentermine, pemoline, phendimetrazine, phenmetrazine, phentermine, prolintane, selegiline, strychnine; and other substances of similar chemical structure of pharmacology effects.

“Doping in sport”, Marina Djordjevic Nikic