Small Pharma Ltd

Cybin UK Ltd

Peter Rands

Zelah Joel

Tiffanie Benway

Marie Claire Layzell

Ellen James

George Knight

Derek Londesbrough

Richard Chubb

Alan Armstrong

Lorraine Sharp

Richard Myerson

Jonathan Hull

Meghan Good

David Pearson

Paul Blaney

Carol Routledge

Marie Layzell

Benjamin Phillips

Trevor Robbins

The present invention relates to aqueous pharmaceutical formulations, methods for their production, and uses thereof. The aqueous pharmaceutical formulations comprise a salt of an optionally substituted dimethyltryptamine compound and water, with a pH from 5 to 6.5, preferably from about 5 to about 6, and a concentration of the optionally substituted dimethyltryptamine compound of about 10 mg/ml or greater as the freebase equivalent. These formulations can comprise an effective dose of an optionally substituted dimethyltryptamine compound for use in psychedelic assisted therapy within a volume of 5 ml or less. Such formulations are surprisingly suitable both for intramuscular injection and nebulised inhalation, being both stable and clinically acceptable, and have potential uses in the treatment of psychiatric or neurological disorders.

Injectable and inhalable formulations

The present invention relates to compounds of formula (I) as defined herein, which comprise a greater proportion of deuterium to protium than naturally found in hydrogen; and compositions, including pharmaceutical compositions, comprising these compounds and optionally analogous compounds of formula (I), which are not deuterium-enriched. These compounds and compositions are of use in therapy, in particular in the treatment of psychiatric or neurological disorders. Varying the amounts of the different compounds within the compositions of the invention allows tailoring of the compositions' therapeutic effects. A particularly efficient synthetic method which enables compounds of formula (I) and related compounds of formula (I′) is also provided.

Deuterated or partially deuterated N,N-dimethyltryptamine compounds

The present invention relates to compounds of formula I, or pharmaceutically acceptable salts thereof, as well as compositions comprising such compounds. These compounds and compositions have uses in the treatment of psychiatric or neurological disorders. Compounds of formula I comprise at least one deuterium atom at the α-position and consequently have improved oral bioavailability relative to α-diprotic analogues.

Compounds

Syntheses of compounds of Formula III from compounds of Formula I via compounds of Formula II are described, as well as particular compounds of Formula III, or pharmaceutically acceptable salts thereof, compositions comprising such compounds, and uses thereof. For example, certain of these compounds and compositions of Formula III have uses in the treatment of psychiatric or neurological disorders.

Synthesis of N,N-dimethyltryptamine-type compounds, methods, and uses

The present invention relates to compositions comprising N,N-dimethyltryptamine, deuterated N,N-dimethyltryptamine and/or partially deuterated N,N-dimethyltryptamine. In particular, the present invention relates to compositions comprising a combination of N,N-dimethyltryptamine and 2% or more by weight of one or more deuterated N,N-dimethyltryptamine compound selected from α,α-dideutero-N,N-dimethyltryptamine and α,α,β,β-tetradeutero-N,N-dimethyltryptamine. Additional and alternative compositions of the present invention comprise a combination of N,N-dimethyltryptamine and 2% or more by weight of one or more partially deuterated N,N-dimethyltryptamine compound selected from α,β,β-trideutero-N,N-dimethyltryptamine, α,β-dideutero-N,N-dimethyltryptamine, and α-deutero-N,N-dimethyltryptamine. Methods of synthesising compositions of the present invention, and methods of use of presently described compositions in treating psychiatric or psychocognitive disorders, such as major depressive disorder, are also provided.

Therapeutic compositions comprising deuterated or partially deuterated N,N-dimethyltryptamine compounds

The present invention relates to a solid dosage form comprising two or more compounds selected from N,N-dimethyltryptamine and its deuterated analogues and pharmaceutically acceptable salts thereof, and methods of treatment (e.g., of a psychiatric disorder or a neurological disorder) comprising administering the solid dosage form to a patient in need thereof.

Therapeutic solid dosage forms

Described herein are compounds of formula (I) as defined herein, which comprise a greater proportion of deuterium to protium than naturally found in hydrogen; and compositions, including pharmaceutical compositions, comprising these compounds and optionally analogous compounds of formula (I), which are not deuterium-enriched. These compounds and compositions are of use in therapy, in particular in the treatment of psychiatric or neurological disorders. Varying the amounts of the different compounds within the compositions of the invention allows tailoring of the compositions' therapeutic effects. A particularly efficient synthetic method which enables compounds of formula (I) and related compounds of formula (I') is also provided.

Deuterated compounds

The present invention relates to compositions comprising N,N-dimethyltryptamine, deuterated N,N-dimethyltryptamine and/or partially deuterated N,N-dimethyltryptamine. In particular, the present invention relates to compositions comprising a combination of N,N-dimethyltryptamine and 2% or more by weight of one or more deuterated N,N-dimethyltryptamine compound selected from &#x3b1;,&#x3b1;-dideutero-N,N-dimethyltryptamine and &#x3b1;,&#x3b1;,&#x3b2;,&#x3b2;-tetradeutero-N,N-dimethyltryptamine. Additional and alternative compositions of the present invention comprise a combination of N,N-dimethyltryptamine and 2% or more by weight of one or more partially deuterated N,N-dimethyltryptamine compound selected from &#x3b1;,&#x3b2;,&#x3b2;-trideutero-N,N-dimethyltryptamine, &#x3b1;,&#x3b2;-dideutero-N,N-dimethyltryptamine, and &#x3b1;-deutero-N,N-dimethyltryptamine. Methods of synthesising compositions of the present invention, and methods of use of presently described compositions in treating psychiatric or psychocognitive disorders, such as major depressive disorder, are also provided.

Therapeutic compounds

Described herein are crystalline fumarate salts having a Formula I, pharmaceutical formulations comprising the same, methods for their production, and uses thereof, Formula I comprising: wherein each Ris independently selected from protium and deuterium; each Ris independently selected from protium and deuterium; each Ris independently selected from protium and deuterium; and each Ris independently selected from protium and deuterium; and wherein the compound has a PXRD pattern comprising characteristic peaks at 19.2&#xb1;0.2 and 24.7&#xb1;0.2 degrees 2-theta.

5-methoxy-N,N-dimethyltryptamine crystalline forms

The present invention relates to compounds of formula (I) as defined herein, which comprise a greater proportion of deuterium to protium than naturally found in hydrogen; and compositions, including pharmaceutical compositions, comprising these compounds and optionally analogous compounds of formula (I), which are not deuterium-enriched. These compounds and compositions are of use in therapy, in particular in the treatment of psychiatric or neurological disorders. Varying the amounts of the different compounds within the compositions of the invention allows tailoring of the compositions' therapeutic effects. A particularly efficient synthetic method which enables compounds of formula (I) and related compounds of formula (I') is also provided. 

Syntheses of compounds of Formula III from compounds of Formula I via compounds of Formula II are described, as well as particular compounds of Formula III, or pharmaceutically acceptable salts thereof, compositions comprising such compounds, and uses thereof. For example, certain of these compounds and compositions of Formula III have uses in the treatment of psychiatric or neurological disorders. 

The present invention relates to compounds of formula I, or pharmaceutically acceptable salts thereof, as well as compositions comprising such compounds. These compounds and compositions have uses in the treatment of psychiatric or neurological disorders. Compounds of formula I comprise at least one deuterium atom at the &#x3b1;-position and consequently have improved oral bioavailability relative to &#x3b1;-diprotic analogues. 

Compounds, compositions, methods, and uses are described for therapeutic deuterated N,N-dimethyltryptamine compounds (e.g., a single compound or a plurality of deuterated N,N-dimethyltryptamine compounds) such as N,N-dimethyltryptamine compounds, &#x3b1;-protio, &#x3b1;-deutero-N,N-dimethyltryptamine compounds, &#x3b1;,&#x3b1;-dideutero-N,N-dimethyltryptamine compounds, and pharmaceutically acceptable salts of these compounds. The deuterated N,N-dimethyltryptamine compound may have an increased half-life compared with the half-life of undeuterated N,N-dimethyltryptamine. For example, a deuterated N,N-dimethyltryptamine compound may be used in therapy and have a Formula (I): 

Deuterated N,N-dimethyltryptamine compounds

The present invention provides novel, stable, processable and pharmaceutically acceptable salt forms of 2R,6R-hydroxynorketamine or 2S,6S-hydroxynorketamine with high aqueous solubility.

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London, United Kingdom

Peter Rands