cerebral blood flow: nootropics and compounds | sci-wiki

Cacao Powder

Cacao powder is the ground, mostly de-fatted solids of the roasted Theobroma cacao bean. Its active fraction is a group of flavanols (flavan-3-ols), chiefly (-)-epicatechin and catechin plus procyanidins, alongside the methylxanthine theobromine and a little caffeine. The flavanols drive nitric-oxide-dependent vasodilation, which is the best-supported reason people take it: lower blood pressure, better endothelial function, and modestly improved blood flow to the brain. Natural (non-alkalized) cacao keeps far more of these flavanols than Dutch-processed cocoa.

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Antivertigo

Betahistine

Betahistine is a histamine analog used as an anti-vertigo medication, most often prescribed for Meniere's disease and related balance disorders. Chemically related to histamine, it acts as a weak agonist at histamine H1 receptors and a stronger antagonist at H3 receptors. It is widely used across Europe and many other countries, although controlled trials have produced mixed evidence for its effectiveness, and it is not approved for general sale in the United States [1][2].

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Nootropic

AWD 52-39

AWD 52-39 is an investigational lysergamide (a chemical relative of LSD) that was developed as a nootropic for cognitive disorders before its discontinuation.

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Nootropic

Bifemelane

Bifemelane (brand names Alnert and Celeport; development code MCI-2016) is a Japanese cerebral activator and antidepressant that acted mainly as a reversible, competitive inhibitor of monoamine oxidase type A, with weaker noncompetitive inhibition of MAO-B [1]. It was prescribed in Japan from the late 1980s for the emotional and cognitive disturbances that follow cerebral infarction [6], and was also trialed in glaucoma [9]. Most of its evidence comes from small Japanese studies from the 1980s and 1990s; it was pulled from the market in 1998 after a national re-evaluation judged the effectiveness of that whole class of cerebral metabolic enhancers to be unproven.

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Nootropic

Indeloxazine

Indeloxazine was developed and marketed in Japan from the late 1980s, under brand names including Elen and Noin, as a dual serotonin/norepinephrine reuptake inhibitor aimed at a use case Western antidepressants of the era largely ignored: the depression, apathy and cognitive slowing that follow a stroke. It stayed almost entirely confined to the Japanese market and pharmacology literature, mechanistically an early dual-reuptake antidepressant that never secured a Western indication despite predating some Western SNRIs. More recently its resolved (+)-isomer, given the separate code AS1069562, has been revisited in Japanese pain research as a serotonin-transporter-mediated analgesic for neuropathic and myalgic pain, giving this obscure Japanese post-stroke drug an unexpected second research life decades later.

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Nootropic

Milameline

Milameline was Parke-Davis and Roussel-Uclaf's shot at treating Alzheimer's disease by stimulating muscarinic receptors directly instead of propping up acetylcholine with a cholinesterase inhibitor. It is a partial agonist with roughly equal affinity at all five muscarinic subtypes, which was the deliberate choice: no subtype selectivity, just enough intrinsic activity to signal without saturating the system. The preclinical package was strong for its era. It reversed spatial memory deficits in rats with lesioned forebrain cholinergic neurons, raised cortical blood flow, desynchronised the EEG in both rats and rhesus monkeys in the pattern that reads as increased arousal, and rescued scopolamine-impaired attention in monkeys. Then the dose window closed. In Alzheimer's patients, 1 mg every six hours was fine, 2 mg was tolerated by most people, and 2.5 to 3 mg brought sweating, hypersalivation, nausea, diarrhoea, hypotension and, notably, parkinsonian signs including cogwheeling, tremor and a shuffling gait; that study was stopped after the fourth 3 mg dose. The pivotal 52-week trial across 38 centres was then terminated early when an interim analysis projected it would not work. It never worked, and it was never approved.

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