JRT

Above: JRT molecular structureBelow: 3D representation of a (+)-JRT molecule
Clinical data
Drug class	Serotonin receptor modulator;Serotonin5-HT2 receptoragonist;Serotonergic psychedelic;Hallucinogen;Psychoplastogen
ATC code	None
Identifiers
IUPAC name (7S)-N,N-diethyl-6-methyl-6,9-diazatetracyclo[7.6.1.02,7.012,16]hexadeca-1(15),2,10,12(16),13-pentaene-4-carboxamide
PubChemCID	166076087
Chemical and physical data
Formula	C20H25N3O
Molar mass	323.440 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCN(CC)C(=O)C1CN([C@@H]2CN3C=CC4=C3C(=CC=C4)C2=C1)C
InChI InChI=1S/C20H25N3O/c1-4-22(5-2)20(24)15-11-17-16-8-6-7-14-9-10-23(19(14)16)13-18(17)21(3)12-15/h6-11,15,18H,4-5,12-13H2,1-3H3/t15?,18-/m1/s1 Key:ZYTVEPYZRGXVRK-KPMSDPLLSA-N

JRT is aserotonin receptor modulator and putativeserotonergic psychedelic andpsychoplastogen related tolysergic acid diethylamide (LSD).^[1][2] It is theanalogue of LSD in which the embeddedtryptaminestructure within theergolinering system of LSD has been replaced with anisotryptamine structure.^[1]

It acts as anon-selective serotonin receptor modulator, including as apartial agonist of the serotonin5-HT_2A receptor and as an agonist orantagonist of various otherserotonin receptors.^[1][2] The drug has psychedelic-like, psychoplastogenic,antipsychotic-like,antidepressant-like, andpro-cognitive effects in animals, whilst lacking apparentpro-psychotic-like effects.^[1][2] It has significant but reduced psychedelic-like effects compared to LSD.^[1][2]

JRT was first described in thescientific literature by 2022.^[1][2] It was developed byDavid E. Olson and colleagues in association withDelix Therapeutics.^[1][2] The drug is being investigated as a possible treatment forschizophrenia.^[1]

In contrast to LSD, (+)-JRT is highlyselective for a subset ofserotonin receptors and does not bind to variousdopamine,adrenergic, orhistamine receptors.^[1] (+)-JRT shows highaffinity for theserotonin5-HT₂ receptors, with K_i values ranging from 2.0 to 184 nM.^[1] It is apotentpartial agonist of the serotonin5-HT_2A and5-HT_2B receptors (E_maxTooltip maximal efficacy = 33–81% and 48–51%, respectively) and afull agonist of the serotonin5-HT_2C receptor (E_max = 89%).[1] The drug is also anagonist of the serotonin5-HT_1A and5-HT₇ receptors, anantagonist of the serotonin5-HT_5A and 5-HT₇ receptors, and binds to the serotonin5-HT₆ receptor.^[1] It does not have significant affinity for the serotonin5-HT_1B or5-HT₃ receptors, whereas the other serotonin5-HT₁ receptors and the serotonin5-HT₄ receptor were not reported.^[1] (+)-JRT is 4.4- to 180-fold less potent than LSD as a serotonin 5-HT_2A receptor agonistin vitro (EC₅₀Tooltip half-maximal effective concentration = 0.4–90 nM vs. 0.09–0.5 nM, respectively) and is lessefficacious than LSD in activating the receptor (E_max = 33% vs. 44–63%, respectively).[1] (+)-JRT dissociates from the serotonin 5-HT_2A receptor approximately 10-fold more quickly than LSD.^[1]

(+)-JRT produces thehead-twitch response (HTR), a behavioral proxy ofpsychedelic effects, in rodents, and hence would be expected to behallucinogenic in humans.^[1] However, the drug shows a reduced HTR compared to LSD, producing less than half the maximal number of head twitches.^[1] It can also antagonize the HTR induced by LSD.^[1] Hence, (+)-JRT may be less psychedelic than LSD in humans.^[1] The drug is similarly potent as LSD in producing the HTR in mice, with the dose producing peak HTR being 0.2 mg/kg in both cases.^[1] (+)-JRT does not affectlocomotor activity and does not produce anyserotonin behavioral syndrome-type effects.^[1] It has been found to inhibitdextroamphetamine-inducedhyperlocomotion in female but not male mice, does not exacerbatephencyclidine (PCP)-induced hyperlocomotion, does not worsendizocilpine (MK-801)-inducedprepulse inhibition (PPI), and does not induce PPI deficits itself.^[1] Some of these findings are in contrast to LSD, and are suggestive that (+)-JRT lackspsychotic-like effects and may haveantipsychotic potential.^[1] In addition to the preceding findings, (+)-JRT has been reported to increaseneuroplasticity and hence to act as apsychoplastogen, to produceantidepressant-like effects, and to promotecognitive flexibility.^[1] It was equivalent with LSD in terms of psychoplastogenic effects.^[1]

JRT is theanalogue of thelysergamidelysergic acid diethylamide (LSD) in which the embeddedtryptaminestructure within theergolinering system of LSD has been replaced with anisotryptamine structure.^[1] Hence, JRT is not an ergoline, lysergamide, or tryptamine itself, but could be considered acyclized isotryptamine.^[1][2] JRT exists as fourenantiomers, including (+)-JRT and (–)-JRT, with (+)-JRT being the active enantiomer.^[1]

JRT was developed by Lee E. Dunlap,David E. Olson, and other colleagues atDelix Therapeutics and theUniversity of California, Davis.^[1][2] It was first described in thescientific literature by 2022.^[1][2]

JRT is being investigated as a possible treatment forschizophrenia.^[1][2]

• List of investigational hallucinogens and entactogens
• List of miscellaneous 5-HT_2A receptor agonists
• IsoDMT
• 6-MeO-isoDMT
• Zalsupindole (DLX-001; AAZ-A-154; (R)-5-MeO-α-methyl-isoDMT)
• DLX-159
• BMB-201
• ITI-1549

• LSD-Inspired Drug Reverses Psychosis Brain Damage Without Hallucinations - Neuroscience News
• Scientists Flip Two Atoms in LSD – And Unlock a Game-Changing Mental Health Treatment - SciTechDaily
• A New Form of LSD to Treat Schizophrenia - Psychology Today

• Drugs not assigned an ATC code
• 5-HT1A agonists
• 5-HT2A agonists
• 5-HT2B agonists
• 5-HT2C agonists
• 5-HT5A agonists
• 5-HT7 agonists
• 5-HT7 antagonists
• Carboxamides
• Diethylamino compounds
• Experimental drugs developed for schizophrenia
• Experimental hallucinogens
• Isotryptamines
• Psychedelic drugs
• Serotonin receptor modulators

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