Bromantane

links: Nootropics reference: 4-24-2021

Bromantane (Ladasten) #

• Primary action: upregulating Tyrosine Hydroxylase and AADC
• GAT-3 inhibitor. PDE10 inhibitor.
• Upregulates Carboxypeptidase E expression R
• Mechanisms of Action of Ladasten: Activation of Gene Expression for Neurotrophins and Mitogen-Activated Kinases
  • This paper suggests the increase in striatum BDNF and following ERK1/2 expression underlies Bromantane’s long-term dopaminergic effects
• Extremely high concentrations inhibit reuptake of of serotonin, dopamine, and to a lesser extent noradrenaline (SNDRI - real) in vitro in rat brain tissue. R R
• Time Course of Histone Deacetylase 1 and Acetylated H3 and H4 Histones in the Brain of Rats Treated with Ladasten
  • A HDAC1 inhibitor: this is a somehow-contentious statement that sirsadalot made based off Amantadine. Maybe the conclusion of these study(s) are wrong.
    • HDAC1 inhibition→GDNF. Amantadine Alleviates Postoperative Cognitive Dysfunction Possibly by Preserving Neurotrophic Factor Expression and Dendritic Arborization in the Hippocampus of Old Rodents
    • This is seen in Memantine as well, and also people’s reports of that GDNF brain fogginess or whatever.
• Has anticholinergic effects: both nicotinic and muscarinic.. in high doses, at least.
• Anti-fibrotic in the kidney and liver.
• Reduced depression-caused inflammation; decresaed the levels of the following inflammatory cytokines.
• “An actoprotector, a substance that makes the body more stable under physical stress without increasing oxygen consumption.”
• Stimulates the immune system; increased B-cell levels.
• Normalizes sleep? Meditative? In patients with redued alpha rhythm, ladasten increased alpha rhythm low frequencies and an increase of Beta waves 1 and 2. For patients with high alpha rhythm, high alpha was increased and a decrease of beta 1 and 2.
  • In patients with neurasthenia characterized by reduced alpha activity combined with emotional lability and inertness.. ladasten was more robust than in patients with prominent alpha rhythm and sthenic personal traits. R
• Maybe inhibits Kir2.1, preventing aberrant synaptogenesis in inhibitory MSNs in the presence of high dopamine.
  • [Inwardly rectifying potassium channels (Reimann 1999)] I believe their blockage facilitates an increase in neuronal intracellular calcium.
  • Sirsad thinks this since amantadine does indeed inhibit Kir2.1
• Anticholinergic effects/metabolites when in very large doses (500mg+ orally)

Effects of ladasten on dopaminergic neurotransmission and hippocampal synaptic plasticity in rats #

• Transforms short-term potentiation of synaptic transmission to a long-lasting form in the hippocampus. Ladasten induces reinforcement of short-term potentiation via protein synthesis and dopamine dependent mechanisms.
• So yeah, major spike in Nucleus Accumbens dopamine. 400% after 2 hours.

Supplementation #

• No withdrawals, dependence, or addiction.
• Timing: ~1-2-4 hours for its action to build up, though it is able to cross the blood brain barrier and can be found in the brain within 10 min after peroral administration at pharmacologically relevant levels R; half-life is ~11.5 hours. Women metablize the drug faster somehow, and it’s ~7 hr for rats and mice.
• Intranasal solution: 90mg/mL in 18mL of Caprylic Acid (1620mg total) for 9mg/spray. 2 sprays is solid?
  • 10-50-100mg sublingually with olive oil. Oral has ~42-50% bioavailability.
  • It is intranasal because when taken orally, activates CYP450 and accumulates in the liver resulting in a 60x elimination constant, reducing the effective half-life. https://www.reddit.com/r/NooTopics/comments/t7zrye/how_is_your_cycle_with_bromantante/