PRL-8-53

PRL-8-53
Clinical data
Routes of; administration	Oral
ATC code	none;
Legal status
Legal status	In general: unscheduled;
Identifiers
	IUPAC name Methyl 3-[2-[benzyl(methyl)amino]ethyl]benzoate;
CAS Number	51352-88-6 ; 51352-87-5 (HCl);
PubChem CID	39988;
ChemSpider	36560;
UNII	BM2TE2XHK6;
CompTox Dashboard (EPA)	DTXSID101350483 ;
Chemical and physical data
Formula	C18H21NO2
Molar mass	283.371 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CN(CCc1cccc(c1)C(=O)OC)Cc2ccccc2;
	InChI InChI=1S/C18H21NO2/c1-19(14-16-7-4-3-5-8-16)12-11-15-9-6-10-17(13-15)18(20)21-2/h3-10,13H,11-12,14H2,1-2H3; Key:IGJQEMHBYKNIQR-UHFFFAOYSA-N;

PRL-8-53 is a nootropic substituted phenethylamine that has been shown to act as a hypermnesic drug in humans; it was first synthesized by medical chemistry professor Nikolaus Hansl at Creighton University in the 1970s as part of his work on amino ethyl meta benzoic acid esters.^[1]^[2]

Mechanism of action

The exact mechanism of action of PRL-8-53 remains unknown. Doses up to 200 mg/kg are not observed to have stimulant properties, and a dosage of 20 mg/kg does not potentiate the effects of dextroamphetamine in rats.^[1] It displays possible cholinergic properties, and potentiates dopamine while partially inhibiting serotonin.^[1] PRL-8-53 reverses the catatonic and ptotic effects of reserpine.^[1]^[3]

Toxicity

PRL-8-53 is relatively non-toxic, with an oral LD₅₀ in mice of 860 mg/kg, giving the drug a high therapeutic index. Doses above 8 mg/kg have brief hypotensive effects in canines. High doses depress motor activity in the rat and mouse, with the ED₅₀ for a 50% reduction in motor activity of mice at 160 mg/kg. PRL-8-53 displays spasmolytic effects.^[3]

Reasons for discontinuation

PRL-8-53's development was not pursued further, despite not exhibiting side effects in human or animal trials that would warrant discontinuation. Termination of further research may have been due to factors including the retirement of Dr. Nikolaus Hansl and a lawsuit filed between Hansl and Creighton University in 1985.

Hansl v. Creighton University

On July 1, 1985 Dr. Nikolaus Hansl entered into a settlement agreement with Creighton University.^[4] The terms of the agreement guaranteed Dr. Hansl access to his laboratory facilities and office space at the university for a period of 2 years.^[4] Upon returning from a 4-month absence. Hansl found that the refrigerator he had used to store various experimental compounds had been unplugged, purportedly rendering the compounds unusable.^[4]

Patent

Dr. Hansl's patent for the synthesis of PRL-8-53 has expired.^[5]

Synonyms

Methyl 3-(2-(benzylmethylamino)ethyl)benzoate hydrochloride
3-(2-benzylmethylaminoethyl) benzoic acid methyl ester hydrochloride
3-(2-(Methyl(phenylmethyl)amino)ethyl)benzoic acid methyl ester hydrochloride

References

^ ^a ^b ^c ^d Hansl NR, Mead BT (April 1978). "PRL-8-53: enhanced learning and subsequent retention in humans as a result of low oral doses of new psychotropic agent". Psychopharmacology. 56 (3): 249–53. doi:10.1007/BF00432846. PMID 418433. S2CID 21036209.
^ US Patent 3870715 A: Substituted amino ethyl meta benzoic acid esters
^ ^a ^b Hansl NR (March 1974). "A novel spasmolytic and CNS active agent: 3-(2-benzylmethylamino ethyl) benzoic acid methyl ester hydrochloride". Experientia. 30 (3): 271–2. doi:10.1007/BF01934822. PMID 4824605. S2CID 918343.
^ ^a ^b ^c "Hansl v. Creighton University". Justia Law. Retrieved 2022-10-16.
^ Nikolaus R. Hansl; Process for hydrolyzing 3-trifluoromethyl phenethylamines (US patent 3 792 048) 1974

[trial-1] Hansl NR, Mead BT (April 1978). "PRL-8-53: enhanced learning and subsequent retention in humans as a result of low oral doses of new psychotropic agent". Psychopharmacology. 56 (3): 249–53. doi:10.1007/BF00432846. PMID 418433. S2CID 21036209.

[2] US Patent 3870715 A: Substituted amino ethyl meta benzoic acid esters

[toxicity-3] Hansl NR (March 1974). "A novel spasmolytic and CNS active agent: 3-(2-benzylmethylamino ethyl) benzoic acid methyl ester hydrochloride". Experientia. 30 (3): 271–2. doi:10.1007/BF01934822. PMID 4824605. S2CID 918343.

[:0-4] "Hansl v. Creighton University". Justia Law. Retrieved 2022-10-16.

[5] Nikolaus R. Hansl; Process for hydrolyzing 3-trifluoromethyl phenethylamines (US patent 3 792 048) 1974

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