Fencamfamine
Encyclopedia
Fencamfamine is a stimulant
which was developed by Merck in the 1960s.
. It released dopamine
by a similar mechanism to amphetamines, but was ten times less potent than dexamphetamine at producing this effect. The main mechanism of action was instead inhibition of dopamine reuptake
. Also unlike amphetamine
s, fencamfamine does not inhibit the action of monoamine oxidase
enzymes. It was concluded that, at least in the models employed, the in vitro profile of fencamfamine is more similar to that of nomifensine
, a reportedly pure uptake inhibitor, than to d-amphetamine.
In animal experiments on place preference fencamfamine produced a significant place preference only at the dose of 3.5 mg/kg. The experiments suggested a relation to dopamine D1 receptors, and also to opioid
receptors in the reinforcement produced by fencamfamine, as place preference was blocked by the selective dopamine D1 antagonist SCH 23390
and by the opioid antagonist naloxone
. A similar place preference, which was blocked by naloxone
and by SCH 23390
and by raclopride
, has been seen in a study on rats with drinking water. Animals treated with naloxone before the conditioning sessions showed a place aversion instead of the place preference found in saline-treated animals. Naloxone also reduced drinking. It was proposed that naloxone induced a state of frustrative nonreward. It was suggested that both dopamine and (endogenous) opioids are important for water-induced reinforcement. Possible interactions between these two neurotransmitter systems were discussed.
Stimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
which was developed by Merck in the 1960s.
Medical uses
Fencamfamine is still used, though rarely, for treating depressive day-time fatigue, lack of concentration and lethargy, particularly in individuals who have chronic medical conditions, as its favourable safety profile makes it the most suitable drug in some cases.Adverse effects
Fencamfamine is well tolerated and causes minimal circulatory effects. Extended use may result in a dryness of the mouth.Contraindications
Not to be used with heart diseases, angina pectoris and decompensated cardiac insufficiency, glaucoma, hyper-excitability and thyrotoxicosis or while treated with monoamine oxidase inhibitors.Overdose
Symptoms of overdose are nausea, agitation and restlessness, dryness of the mouth, dizziness and tremor. In gross overdosage also associated with dyspnoea, tachycardia, disorientation and convulsions.Research
In a study on slices of rat corpus striatum and substantia nigra fencamfamine acted as an indirect dopamine agonistDopamine agonist
A dopamine agonist is a compound that activates dopamine receptors in the absence of dopamine. Dopamine agonists activate signaling pathways through the dopamine receptor and trimeric G-proteins, ultimately leading to changes in gene transcription.-Uses:...
. It released dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
by a similar mechanism to amphetamines, but was ten times less potent than dexamphetamine at producing this effect. The main mechanism of action was instead inhibition of dopamine reuptake
Reuptake
Reuptake, or re-uptake, is the reabsorption of a neurotransmitter by a neurotransmitter transporter of a pre-synaptic neuron after it has performed its function of transmitting a neural impulse....
. Also unlike amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
s, fencamfamine does not inhibit the action of monoamine oxidase
Monoamine oxidase
L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase...
enzymes. It was concluded that, at least in the models employed, the in vitro profile of fencamfamine is more similar to that of nomifensine
Nomifensine
Nomifensine is a norepinephrine-dopamine reuptake inhibitor developed by a team at Hoechst AG in the 1960s.. The drug was test-marketed in the United States by Hoechst AG , i.e. a drug that increases the amount of synaptic norepinephrine and dopamine available to receptors by blocking the dopamine...
, a reportedly pure uptake inhibitor, than to d-amphetamine.
In animal experiments on place preference fencamfamine produced a significant place preference only at the dose of 3.5 mg/kg. The experiments suggested a relation to dopamine D1 receptors, and also to opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
receptors in the reinforcement produced by fencamfamine, as place preference was blocked by the selective dopamine D1 antagonist SCH 23390
SCH 23390
SCH23390 is a synthetic compound that acts as a D1 receptor antagonist and has either minimal or negligible effects on the D2 receptor....
and by the opioid antagonist naloxone
Naloxone
Naloxone is an opioid antagonist drug developed by Sankyo in the 1960s. Naloxone is a drug used to counter the effects of opiate overdose, for example heroin or morphine overdose. Naloxone is specifically used to counteract life-threatening depression of the central nervous system and respiratory...
. A similar place preference, which was blocked by naloxone
Naloxone
Naloxone is an opioid antagonist drug developed by Sankyo in the 1960s. Naloxone is a drug used to counter the effects of opiate overdose, for example heroin or morphine overdose. Naloxone is specifically used to counteract life-threatening depression of the central nervous system and respiratory...
and by SCH 23390
SCH 23390
SCH23390 is a synthetic compound that acts as a D1 receptor antagonist and has either minimal or negligible effects on the D2 receptor....
and by raclopride
Raclopride
Raclopride is a synthetic compound that acts as an antagonist on D2 dopamine receptors.It can be radiolabelled with the carbon-11 radioisotope and used in positron emission tomography scanning to assess the degree of dopamine binding to the D2 Dopamine receptor.For example, one study found...
, has been seen in a study on rats with drinking water. Animals treated with naloxone before the conditioning sessions showed a place aversion instead of the place preference found in saline-treated animals. Naloxone also reduced drinking. It was proposed that naloxone induced a state of frustrative nonreward. It was suggested that both dopamine and (endogenous) opioids are important for water-induced reinforcement. Possible interactions between these two neurotransmitter systems were discussed.