KM-391 explained

Routes Of Administration:Oral
Class:Serotonin reuptake inhibitor
Synonyms:KM391

KM-391 is a serotonin reuptake inhibitor which was under development for the treatment of autism but was never marketed.[1] [2] [3] [4] [5] It is taken by mouth.

Description

The drug showed activity in an animal model of autism. In this model, the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) is injected into the forebrain of newborn rat pups and this results in neonatal serotonin depletion, development of autism-like behaviors, and reduced neuroplasticity. KM-391 was able to restore brain serotonin concentrations to near-normal levels, restore normal behaviors, and increase neuroplasticity. Moreover, it was more efficacious than fluoxetine in this model. KM-391 also diminished the intensification of autism-like behaviors, such as repetitive behaviors and sensitivity to touch, that occurred when an oxytocin receptor antagonist was added in the model.

KM-391 was under development by Cellceutix Corporation (now Innovation Pharmaceuticals). It remained under development as late as 2012 and reached the preclinical research stage of development for autism. However, its development was eventually suspended.

See also

Notes and References

  1. Web site: Research programme: autism therapeutic (KM-391) - Innovation Pharmaceuticals . AdisInsight . 9 June 2017 . 10 November 2024 . Cellceutix (now Innovation Pharmaceuticals) was developing KM 391, an orally active, small molecule serotonin uptake modulator, for the treatment of autism. [...] .
  2. Web site: Delving into the Latest Updates on KM-391 with Synapse . Synapse . 1 November 2024 . 10 November 2024.
  3. Webb S . Drugmakers dance with autism . Nat Biotechnol . 28 . 8 . 772–774 . August 2010 . 20697394 . 10.1038/nbt0810-772 . Cellceutix, a biotech company in Beverly, Massachusetts, is also testing a preclinical compound for autism, KM-391, in a rodent model of autism developed by researchers at the Kennedy Krieger Institute in Baltimore. The autism-like symptoms are induced by injecting the chemical 5,7-dihydroxytryptamine (5,7-DHT) into the forebrain of newborn rat pups, leading to neonatal serotonin depletion, reduced brain plasticity and abnormal behaviors. In an initial study, KM-391 given over 90 days restored normal behaviors, and near-normal serotonin levels and increased brain plasticity relative to a nontreatment group and a group given Prozac. Another study measuring serotonin levels in three regions of the rat brain has confirmed the restoration of normal serotonin levels. Another small study added an oxytocin antagonist to the mix. The antagonist alone intensified the autism-related behaviors, such as repetitive behaviors and sensitivity to touch, but when given with KM-391, the frequency and intensity of these behaviors were reduced. .
  4. Kumar B, Prakash A, Sewal RK, Medhi B, Modi M . Drug therapy in autism: a present and future perspective . Pharmacol Rep . 64 . 6 . 1291–1304 . 2012 . 23406740 . 10.1016/s1734-1140(12)70927-1 . Tab. 3. Drugs under different phases of development #: [...] [Drug:] KM 391: Action: Acts on serotonin uptake. Developmental stage: Preclinical stage. [...] # Source: http://clinicaltrials.gov/.
  5. Majhi S, Kumar S, Singh L . A Review on Autism Spectrum Disorder: Pathogenesis, Biomarkers, Pharmacological and Non-Pharmacological Interventions . CNS Neurol Disord Drug Targets . 22 . 5 . 659–677 . 2023 . 36915952 . 10.2174/1871527321666220428134802 .

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