Ibogaine analogs as therapeutics for neurological and psychiatric disorders
Inventors
Sames, Dalibor • Havel, Vaclav
Assignees
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Publication Number
US-12564597-B2
Publication Date
2026-03-03
Expiration Date
Abstract
The present invention provides a composition which comprises a compound which is a mixture of deuterium containing and non-deuterium containing molecules having the structure:wherein R1 iswherein at least one of H1, H2 or H3 is a deuterium-enriched —H site, orwherein at least one of H1, H2, H3, H4 or H5 is a deuterium-enriched —H site, or a pharmaceutically acceptable salt of the compound, and methods of using the composition to treat pain, depressive disorders, mood disorders, anxiety disorders, opioid use disorders, and opioid withdrawal symptoms.
Core Innovation
The invention concerns deuterium-containing and non-deuterium-containing molecules having a specified structure in which at least one of H1, H2, or H3 is a deuterium-enriched —H site, or at least one of H1, H2, H3, H4, or H5 is a deuterium-enriched —H site. The compounds include deuterium-containing analogs of ibogaine-related compounds, including CD3O-ibogamine and related isotopologues and hydrochloride analogs, with optional pharmaceutically acceptable salts and carriers.
In the mixture, the level of deuterium at a deuterium-enriched —H site is 20%-100%, or the proportion of molecules having deuterium at the deuterium-enriched H-position is substantially greater than 0.0156% of molecules in the mixture. The disclosure also presents the compounds as pharmaceutical compositions that include a pharmaceutically acceptable carrier, and in some embodiments further include a mu-opioid receptor agonist and an opioid or opiate.
The patent further describes biological stability and metabolism of CD3O-ibogamine relative to ibogaine in human liver microsomes and rat liver microsomes, as well as in vivo pharmacokinetics in rats. It reports noribogaine formation, plasma pharmacokinetics, brain distribution, and plasma noribogaine exposure, and links the deuterium-containing compounds to an improved therapeutic window via attenuated noribogaine formation.
Claims Coverage
The provided set includes three independent claims. Collectively, they cover a deuterium-enriched mixed-molecule composition defined by deuterium level or proportion at specified H positions, a pharmaceutical composition with a carrier and a deuterium-enriched compound with a deuterium threshold, and a systemic in vivo delivery method using such a carrier/composition to deliver a first compound.
Deuterium-enriched mixture at specified H sites with defined deuterium level or proportion
A composition comprising a mixture of deuterium containing and non-deuterium containing molecules having the structure, wherein at least one of H1, H2 or H3 is a deuterium-enriched —H site and the level of deuterium at any one of the deuterium-enriched —H sites is 20%-100%, or wherein at least one of H1, H2, H3, H4 or H5 is a deuterium-enriched —H site and the proportion of molecules having deuterium at the at least one of H1, H2, H3, H4 or H5 position is substantially greater than 0.0156% of molecules in the mixture, or a pharmaceutically acceptable salt of the compound.
Deuterium-enriched compound in a carrier composition with a ≥50% deuterium threshold
A composition comprising a carrier and a compound having the structure, wherein at least one of H1, H2 or H3 is a deuterium-enriched —H site, or wherein at least one of H1, H2, H3, H4 or H5 is a deuterium-enriched —H site, wherein the level of deuterium at any one of the deuterium-enriched —H sites of the deuterium containing molecules is no less than 50%, or a pharmaceutically acceptable salt of the compound.
Systemic in vivo delivery using a carrier composition with deuterium-enriched H sites
A method for systemic in vivo delivery of a first compound having the structure to a subject, the method comprising administering to the subject a composition which comprises a carrier and a second compound having the structure, wherein at least one of H1, H2 or H3 is a deuterium-enriched —H site; and wherein the level of deuterium at any one of the deuterium-enriched —H sites is 20%-100%, or wherein at least one of H1, H2, H3, H4 or H5 is a deuterium-enriched —H site, or a pharmaceutically acceptable salt of the compound, so as to thereby deliver the first compound to the subject.
Across the independent claims, the inventive coverage centers on deuterium-enriched —H sites at specified hydrogen positions within defined structures, combined with quantitative deuterium level or proportion thresholds, and optionally implemented as pharmaceutical compositions and as systemic in vivo delivery methods that deliver a first compound to a subject.
Stated Advantages
Improved therapeutic window via attenuated noribogaine formation.
Altering a subject’s psychological state.
Enhancing psychotherapy effects.
Inducing wakefulness or decreasing sleepiness.
Inducing a central stimulating effect.
Reducing REM sleep duration.
Providing energetic feelings.
Alleviating opioid withdrawal symptoms.
Addressing opioid use disorder, alcohol use disorder, and stimulant use disorder.
Treating depressive/mood/anxiety disorders.
Addressing Parkinson’s disease.
Addressing traumatic brain injury.
Providing pain relief with opioid/opiate co-administration.
Documented Applications
Systemic in vivo delivery of a first compound to a subject using a composition comprising a carrier and a deuterium-enriched second compound, to thereby deliver the first compound to the subject.
Altering a subject’s psychological state.
Enhancing psychotherapy effects.
Inducing wakefulness or decreasing sleepiness.
Inducing a central stimulating effect.
Reducing REM sleep duration.
Producing energetic feelings.
Treating opioid withdrawal symptoms and use contexts for opioid use disorder.
Treating alcohol use disorder.
Treating stimulant use disorder.
Treating depressive disorder, mood disorder, and anxiety disorder.
Treating Parkinson’s disease.
Treating traumatic brain injury.
Treating pain with opioid/opiate co-administration.
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