George Lesher was a chemist, working for the Sterling-Winthrop Research Institute in Rensselaer, New York. While working on antibiotic development with coworkers, two unintended events lead to two unique discoveries. These were the introductions of quinolone antibiotics and an extremely strong stimulant called amfonelic acid.

The research group was exploring the antimalarial drug chloroquine. An impure batch was received from their chemical supplier, this impurity still exhibited antimicrobial activity. Although this impurity did not display significant therapeutic effects, its derivatives were further explored.

The derivations of this chemical led to the development of Nalidixic acid as an effective and later commercialized anti-biotic.[1] Further exploration found nalidixic acid derivatives to be either central nervous system stimulants or depressants.

The one compound that stuck out was amfonelic acid (AFA). This specific structure became a focus due to its dopaminergic activity which displayed greater dopaminergic activity than both cocaine and amphetamine.

This random error of synthesis and pursuit of anti-microbial compounds led to the discovery of quinolone anti-biotics and a unique class of dopaminergic agents.

Amfonelic acid (AFA) stood out due to its pronounced dopaminergic interaction. AFA induces a significant increase in locomotor activity similar in many ways to amphetamine and cocaine. It is a dopamine reuptake inhibitor (DRI) which is 50 times stronger than cocaine.[2]

Amfonelic Acid Pharmacology

Amfonelic acid is a strong locomotor stimulant, this has been displayed in a variety of animal models. [3] AFA primarily acts on dopamine with some serotonergic action as well.

Amfonelic acid produces similar stimulant effects to amphetamines. However, these effects are elicited through unique pathways.

AFA promotes dopamine release by targeting older synthesized dopamine stores. It does so in an “impulse-induced” manner similar to the compound BPAP. This means that response to stimulatory events will produce pronounced dopamine response. These dopaminergic characteristics of Amfonelic Acid differ from amphetamine in that: amphetamine targets the release of newly synthesized dopamine and causes non-impulse-dependent dopamine increases in select regions of the brain. [4]

At doses above 1mg/kg in animals, AFA displayed increases of serotonin (5-HT) synthesis in the brain. Research by P. C. Waldmeier et. Al reported increases in tryptophan (TRYP) and 5-hydroxyindoleacetic acid (5-HIAA).

TRYP is a substrate for serotonin synthesis and 5-HIAA is a metabolite of serotonin. Increases in both compounds are indicative of increased synthesis and levels of serotonin in the brain.

The increases in TRYP and 5-HIAA were not altered by administration of the dopamine agonist haloperidol. This means the effects on 5-HT are independent of AFA’s dopaminergic actions.

There has been no evidence of effects on noradrenaline transmission. Research shows AFA to be preferential to dopamine with some 5-HT interactions. [6]

Amfonelic Acid Side effects

Amfonelic acid has no established use in household, veterinary, medical, or any other manner. I was unable to find any human data on exposure to AF. The compound has appeared on several “grey market research chemical” sites and is available from legitimate chemical companies for laboratory use.

There are anecdotal accounts of consumption of AF for recreational purposes. Users acquired the compound through research chemical sites and administered it to themselves, ignoring its intended use and safety issues.

Websites such as Bluelight.org and Reddit.com display user accounts of the compound. Many reports describe a unique, very enjoyable, perceived dopamine response which is free from norepinephrine side effects. The dosage range from mild to strong seems to be extremely small.

Though users enjoyed the compound and reported no epinephrine effects, some users have reported significant side effects such as:

· Numbness in Extremities

· Sleep Interruptions

· Breathing Abnormalities

· Brain Zapps

· Alteration in Body Temperature

· Paranoia

· Addiction

Amfonelic Acid Dosage

There is no safe or recommended amfonelic acid dose like there is with a prescription dopaminergic drug like modafinil. As previously mentioned there has been no agency approval or safety data for this compound. The only information that exists is from self-experimenting users reports. Even these reports must be taken lightly as there is no proof of their validity.

Internet accounts report doses of 10mg-30mg, with 10mg being very mild and 30mg being extremely strong.

Amfonelic Acid Use Reports

Like amfonelic acid dosage and use there is no large-scale data, only a small number of anecdotal accounts exist.

A quick search only yields 3 reports which address AF being used without other substances. Single application oral use around 25mg seems to be tolerated with little side effects. Whereas habitual and abusive doses produced moderate to significant side effects.

There is also a very large addiction potential for this compound. One user reported continued use even after notable negative side effects, perhaps this speaks to the addictive nature of the compound. [7]

1. The first reports an administration of 25mg AFA along with 1000mg L-Tyrosine no side effects except an elevated resting heart rate of 100BPM. There was little to no euphoria, notable mood elevation, and significant productivity. Reddit: First Time Trying Amfonelic Acid

2. Another report; a user administered one oral dose estimated at 20mg, one intranasal dose at 20mg, and another unmeasured intranasal application described as “another bump, probably about double what I did before.” The user claimed to have a pleasant experience until the third, large administration.” The first two applications provided the following experience: “Maybe the closest I've gotten was the first time I did meth (crazy euphoric, "in the zone", focused) but without the euphoria. It's a very bizarre feeling that I think only a drug of this type can produce.” Reddit: Amfonelic Acid Experience

3. A third user reported taking an initial 10mg oral dose which yielded little euphoria and mild stimulation/motivation without side effects. He then went on to take 20mg/day for 3 days, on the third day the user developed high fever nausea and cough. AFA use was then discontinued for 2 weeks. After the week abstinence he went on to take AFA orally at 25mg doses. This was administered 8-10 times within a 2-month period. During this time the user experienced numbness in face and extremities accompanied, sleep interruptions, and depressed breathing. These side effects did subside after discontinuing. Despite the significant negative side effects the user did enjoy the benefits of the stimulant. Reddit Nootropics: Amfonelic Acid Dangers

4. Another user which administered several doses exceeding 50mg commented on this post and claimed significant negative side effects without any stimulation. There is a possibility this user did not actually receive AFA. He experienced depression of breathing, brain zaps, and extreme increase in body temperature. Reddit: Brain Zapps, Breathing, and Body Temperature

5. Another post reported psychosis when using 1g of AFA per week along with a cocktail of other compounds. OP posted the following about his brother “he is 28 years old 180lbs has been taking Amfonelic acid, Tianeptine (abusing it), noopept, phenibut and Phenethylamine. he is also prescribed/on zoloft and klonopin. what worries me is his dosage of amfonelic-acid, he has gone through 1 gram in a week and has been taking it for 2 weeks. his mental delusions are the worst and involve themes of paranoia he is also having audible hallucinations and minor visuals.” Reddit: Polydrug Psychosis

Benefits of Amfonelic Acid

The discussion of benefits may seem odd with the uncertain nature of this compound. However, some smarter than me have said “The dose makes the medicine or makes the poison.”

I had approached this article expecting to study an extremely harmful compound. However, some of the high-level research has shown possible neuroprotective effects. Though there were some anecdotal reports of very bad side effects; there were also very notable focus, mood, and energy benefits as well.

Amfonelic acid protected against negative chemical and biological side effects induced by Methamphetamine in a rat model. Methamphetamine induces destruction of dopaminergic nerve terminals and the promotion of astrogliosis in the neostriatum. It does so by blocking the dopamine transporter as it is a reuptake inhibitor.

AF was able to completely ameliorate these effects aside from astrocytes in the ventral-lateral neostriatum. This area experiences the greatest dopamine depletion with methamphetamine use. [8]

Methamphetamine administration suppresses both tryptophan and tyrosine hydroxylase enzymatic activity. The coadministration of AF with MA maintained both of their activity. [9]

Conclusion

Amfonelic acid is nothing short of interesting. It is a compound that exists in the outer stratosphere of research chemicals. It seems to harness both unique benefits with extreme danger. It’s enticing characteristics on paper are defended by a cover of unforgiving spines. Cheers to a compound few have known, and the majority will not.