DEMPDHPCA

DEMPDHPCA
Clinical data
Other names	"Compound 160a"
Drug class	Serotonin 5-HT2 receptor agonist; Simplified/partial LSD analogue
Identifiers
	IUPAC name N,N-diethyl-1-methyl-5-phenyl-3,6-dihydro-2H-pyridine-3-carboxamide;
PubChem CID	156277299;
Chemical and physical data
Formula	C17H24N2O
Molar mass	272.392 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCN(CC)C(=O)C1CN(CC(=C1)C2=CC=CC=C2)C;
	InChI InChI=1S/C17H24N2O/c1-4-19(5-2)17(20)16-11-15(12-18(3)13-16)14-9-7-6-8-10-14/h6-11,16H,4-5,12-13H2,1-3H3; Key:DRQYLJPWAXRRHI-UHFFFAOYSA-N;

DEMPDHPCA is a serotonin 5-HT₂ receptor agonist and a cyclized phenethylamine and simplified or partial ergoline that is structurally related to the serotonergic psychedelic lysergic acid diethylamide (LSD).^[1]^[2]^[3] It is the analogue of LSD in which the carbon and nitrogen atoms at positions 1 through 4 of the ergoline ring system have been removed.^[1]^[2]^[3]

Pharmacology

DEMPDHPCA produces gross behavioral effects very similar to those of psychedelics like LSD in rodents and has been assumed to act as a hallucinogen likewise.^[1] However, the drug has not been tested in humans.^[1] DEMPDHPCA is much less potent than LSD in rodents, which was active at a dose of 0.16 μmol/kg by intraperitoneal injection, whereas DEMPDHPCA was active at doses of 10 to 35 μmol/kg.^[1] On the other hand, DEMPDHPCA was more potent than dimethyltryptamine (DMT) and is more potent than mescaline.^[1]

Like LSD, the drug has been found to act as a potent serotonin 5-HT_2A and 5-HT_2C receptor agonist in vitro.^[2] The affinities (IC₅₀Tooltip half-maximal inhibitory concentration) of the more active enantiomer are in the ranges of 10–100 nM for the serotonin 5-HT_2A receptor and 100–1,000 nM for the serotonin 5-HT_2C receptor, while its activational potencies (EC₅₀Tooltip half-maximal effective concentration) are less than 100 nM for the serotonin 5-HT_2A receptor and in the range of 10–100 nM for the serotonin 5-HT_2C receptor.^[2] The more active enantiomer of DEIMDHPCA was among the most potent serotonin 5-HT_2A receptor agonists of 27 evaluated ergoline-like compounds.^[2]

History

DEMPDHPCA was first described in the scientific literature by Mangner in 1978.^[1] It was subsequently patented in 2021 by David E. Olson and colleagues and the patent was assigned to Delix Therapeutics.^[2]

Derivatives

A few derivatives of DEMPDHPCA have also been studied and found to produce similar effects and/or amphetamine-like in animals, including the derivatives with 4-methoxy- and 3,4,5-trimethoxy- substitutions on the phenyl ring and the derivative with the phenyl ring replaced with a 1-naphthalene ring.^[1] The former two were less potent than DEMPDHPCA, whereas the latter was slightly more potent.^[1] Another derivative of DEMPDHPCA, synthesized by David E. Nichols and described in his thesis, is DEMPDHPCA-2C-D, the derivative with 4-methyl and 2,5-dimethoxy substitutions on the phenyl ring.^[4]

Chemical structures of DEMPDHPCA derivatives

DEMPDHPCA-PMA (4-methoxyphenyl-)^[1]
DEMPDHPCA-mescaline (3,4,5-trimethoxyphenyl-)^[1]
DEMPDHPCA-NAP (1-naphthalenyl-)^[1]
DEMPDHPCA-2C-D (4-methyl-2,5-dimethoxyphenyl-)^[4]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l Mangner TJ (1978). Potential Psychotomimetic Antagonists. N,n -diethyl-1-methyl-3-aryl-1, 2, 5, 6-tetrahydropyridine-5-carboxamides (Ph.D. thesis). University of Michigan. doi:10.7302/11268. Archived from the original on 30 March 2025. The gross behavior of the test animals under the influence of 160a-d was observed during the course of the dose-response study depicted by Figure 7. The gross behavioral signs displayed by rats under the influence of the phenyl (160a) and trimethoxyphenyl (160c) homologs were indistinguishable from those exhibited with LSD, DMT or mescaline, and were characterized by general inactivity, muscle twitching and the occurrence of a Straub tail reaction (a somewhat specific indication of the influence of a psychotomimetic drug in which the tail is held in an upright 191 position ). The naphthyl homolog (160d) produced similar behavioral signs but the rats were more active than with 160a and 160c. The gross behavioral pattern of rats under the influence of the methoxy homolog (160b), in contrast, was not at all similar to that caused by LSD, 160a or 160c. It more closely resembled the pattern exhibited with amphetamine, characterized by very marked hyperactivity. [...] Initial indications, based on the gross behavioral comparisons mentioned previously, are that 160a,c,d possess psychotomimetic activity similar to LSD, while 160b possesses amphetamine-like stimulatory activity. [...] On the other hand, 160a, whose structure more closely resembles that of LSD, seems to have LSD-like activity of greater potency than either 160b or 160c. Since the structure of 160a is very closely related to the structure of LSD and contains no aryl methoxy groups necessary for psychotomimetic activity in the methoxyamphetamine series, it could be inferred that 160a acts via an LSD-like mechanism. [...] SUMMARY [...]
^ ^a ^b ^c ^d ^e ^f WO 2021076572, Olson DE, Dunlap L, Wagner F, Chytil M, Powell NA, "Ergoline-like compounds for promoting neural plasticity", published 22 April 2021, assigned to Delix Therapeutics, Inc. and The Regents of the University of California
^ ^a ^b "N,N-diethyl-1-methyl-5-phenyl-3,6-dihydro-2H-pyridine-3-carboxamide". PubChem. Retrieved 1 April 2025.
^ ^a ^b Nichols DE (May 1973). Potential Psychotomimetics: Bromomethoxyamphetamines and Structural Congeners of Lysergic Acid (Thesis). University of Iowa. p. 23. OCLC 1194694085.

External links

DEMPDHPCA - Isomer Design

[Mangner1978-1] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l Mangner TJ (1978). Potential Psychotomimetic Antagonists. N,n -diethyl-1-methyl-3-aryl-1, 2, 5, 6-tetrahydropyridine-5-carboxamides (Ph.D. thesis). University of Michigan. doi:10.7302/11268. Archived from the original on 30 March 2025. The gross behavior of the test animals under the influence of 160a-d was observed during the course of the dose-response study depicted by Figure 7. The gross behavioral signs displayed by rats under the influence of the phenyl (160a) and trimethoxyphenyl (160c) homologs were indistinguishable from those exhibited with LSD, DMT or mescaline, and were characterized by general inactivity, muscle twitching and the occurrence of a Straub tail reaction (a somewhat specific indication of the influence of a psychotomimetic drug in which the tail is held in an upright 191 position ). The naphthyl homolog (160d) produced similar behavioral signs but the rats were more active than with 160a and 160c. The gross behavioral pattern of rats under the influence of the methoxy homolog (160b), in contrast, was not at all similar to that caused by LSD, 160a or 160c. It more closely resembled the pattern exhibited with amphetamine, characterized by very marked hyperactivity. [...] Initial indications, based on the gross behavioral comparisons mentioned previously, are that 160a,c,d possess psychotomimetic activity similar to LSD, while 160b possesses amphetamine-like stimulatory activity. [...] On the other hand, 160a, whose structure more closely resembles that of LSD, seems to have LSD-like activity of greater potency than either 160b or 160c. Since the structure of 160a is very closely related to the structure of LSD and contains no aryl methoxy groups necessary for psychotomimetic activity in the methoxyamphetamine series, it could be inferred that 160a acts via an LSD-like mechanism. [...] SUMMARY [...]

[WO2021076572-2] ^ ^a ^b ^c ^d ^e ^f WO 2021076572, Olson DE, Dunlap L, Wagner F, Chytil M, Powell NA, "Ergoline-like compounds for promoting neural plasticity", published 22 April 2021, assigned to Delix Therapeutics, Inc. and The Regents of the University of California

[PubChem-3] "N,N-diethyl-1-methyl-5-phenyl-3,6-dihydro-2H-pyridine-3-carboxamide". PubChem. Retrieved 1 April 2025.

[Nichols1973-4] Nichols DE (May 1973). Potential Psychotomimetics: Bromomethoxyamphetamines and Structural Congeners of Lysergic Acid (Thesis). University of Iowa. p. 23. OCLC 1194694085.

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