Over the last few decades, the pharmaceutical industry has developed and marketed a multitude of stimulant drugs that were originally designed to treat problems such as fatigue and tiredness, appetite suppression or lack of concentration.

However, over time some drugs have created problems of abuse and dependency, and have been withdrawn or banned in certain areas. This is the case with fencamfamin, a drug with stimulant properties that is currently on a list of medicines banned in sport.

We will now discuss the properties and clinical uses of fencamfamin , its mechanism of action, adverse reactions and contraindications, as well as its effects on the psychological mechanism of latent inhibition.

Phencamphamin: description and clinical uses

Fencamphamin is a drug with mild stimulating effects on the central nervous system . It was developed by the German pharmaceutical company Merck in the 1960s as a drug indicated for appetite suppression, although it was later withdrawn because of the dependency and abuse problems it caused. Its effects are approximately half as potent as those of dextroamphetamine.

Fencamphamin has been used to treat daytime fatigue, lack of concentration and lethargy, and is especially useful in patients with chronic conditions, due to its favorable safety profile. The drug was marketed under the names “Reactivan” and “Glucoenergan”, and was initially quite popular in the field of sports, specifically among athletes and runners, since its invigorating effects were in high demand in the locker rooms of many teams and sportsmen.

This stimulant medication has been attributed a significant potential for abuse, due to its psychoactive reinforcing effects and its mechanism of action, since it acts on dopaminergic receptors and the reward system. In this sense, one of the best known cases of abuse of this substance was the 1978 World Cup in Argentina, where the footballer Willie Johnston tested positive for fencamfamin when he was tested for doping.

This substance is still today included in the list of substances prohibited in sport within the category of specific stimulants. Fencamphamin is still marketed in some countries and is still prescribed as a stimulant drug for patients with fatigue and asthenia . In addition, research on its therapeutic effects on narcolepsy continues.

Mechanism of action

Fencamphamin acts as an indirect dopamine agonist drug . The mechanism of action of this drug involves the release of this neurotransmitter by a procedure similar to that of amphetamines, although the main mechanism is inhibition of dopamine reuptake.

Furthermore, unlike amphetamines, fencamfamin does not inhibit the action of the enzyme monoamine oxidase, which is involved in the elimination of dopamine, noradrenaline and serotonin, which allows more neurotransmitters to be available at the synapses to exert the pharmacological effects on the target receptors. In fact, studies have shown that the in vitro profile of fencamfamin is more similar to that of nomifensin, a drug that inhibits the reuptake of dopamine and noradrenaline, than to that of d-amphetamine.

In animal research on site preference conditioning (a model used to study the motivational properties of certain psychoactive substances) it has been observed that phencamphamin produces a significant site preference only at a particular dose (around 3.5 mg/kg).

In addition, the experiments suggest that this drug could act on dopamine D1 receptors, and also on opioid receptors, since site preference is blocked by a selective dopamine D1 antagonist (SCH-23390) and by an opioid antagonist (naloxone).

Adverse reactions and contraindications

The behavioural effects of stimulants are very similar to each other and include increased blood pressure and breathing rate, and increased heart rate. However, fencamfamin is fairly well tolerated and does not produce significant circulatory effects , although prolonged use may cause dry mouth.

It should be noted that this drug should not be used if you have heart disease, angina, decompensated heart failure, glaucoma, hyperexcitability, thyrotoxicosis, or while being treated with monoamine oxidase inhibitor (MAOI) drugs.

On the other hand, excessive use of fencamfamin or an overdose can cause symptoms such as the following:

  • Agitation
  • Dry mouth
  • Restlessness
  • Dizziness
  • Tremors
  • Dyspnea
  • Tachycardia
  • Disorientation
  • Seizures

Effects of Fencamphamin on latent inhibition

Latent inhibition is a psychological mechanism that people develop and that allows us to filter out the stimuli in our environment that we perceive as irrelevant based on our particular experience. This ability to “separate the wheat from the chaff”, or in other words, to capture only the information that is really relevant and necessary in a given situation, makes it much easier for us to function in our daily lives.

But not all individuals are able to inhibit irrelevant stimuli with the same effectiveness. People with low latent inhibition are unable to abstract a large amount of unnecessary stimuli that produce a volume of information that exceeds their cognitive resources, generating high levels of stress and frustration.

Studies have shown that fencamfamin blocks the latent inhibitory effect at doses of 3.5 mg/kg. A latent inhibitory effect that research suggests may be mediated by the mesolimbic dopamine system. This makes sense since, as we have previously mentioned, fencamfamin acts by inhibiting the reuptake of dopamine, causing an increase in the levels of this neurotransmitter in the nucleus accumbens and the striatum.

On the other hand, it has been found that at higher doses (around 7 mg/kg) fencamfamin does not block latent inhibition. And given that this drug produces stereotyped behaviour at high doses , it is possible that the unconditioned stereotyped responses generated by these doses interfere with the behavioural processes that occur in the conditioning phase of latent inhibition.

Bibliographic references:

  • Aizenstein, M. L., Segal, D. S., & Kuczenski, R. (1990). Repeated amphetamine and fencamfamine: Sensitization and reciprocal cross-sensitization. Neuropsychopharmacology.
  • Alves, C. R., Delucia, R., & Silva, M. T. A. (2002). Effects of fencamfamine on latent inhibition. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 26(6), 1089-1093.
  • Gorenstein, C., DeLucia, R., & Gentil, V. (1988). Efectos psicoestimulantes de la fencanfamina en voluntarios sanos. Revista Brasileña de Investigación Médica y Biológica, 21(3), 475-477.