Methylphenidate

links: Drugs reference: https://www.youtube.com/watch?v=EIgISomLl1o 5-6-2021

Methylphenidate #

2-4 hours instant release is Ritalin; 3-8 hours sustained release is Ritalin SR; 8-12 hours for extended release is Concerta.

• DNRI.
  • Or rather, an inverse agonist of DAT? Not a silent antagonist like I think I’ve heard bupropion, or modafinil, characterized as.
• Dysregulates κ-Opioid Receptor

The subjective effects are really lowkey compared to adderall. You hardly notice it sometimes.

• Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function .32mg/kg oral HED, aka ~23mg which really isn’t low at all. It’s sold in the 5-72mg range.

Dexmethylphenidate (Focalin) #

• AKA d-threo-methylphenidate (D-TMP).
• 4-6 hour duration. Focalin XR = 12 hours.
• Less peripheral, racy, and anxiogenic effects.
• Marginal releasing agent?
• Should be ~2x as strong. More dopaminergic overall, I believe. I think that makes it significantly euphoric.

Chronic Use/Widthdrawals #

• Remind me again why this is toxic? Is it even?? (only bad thing I know I suppose is dependency)
  • Methylphenidate and brain dopamine neurotoxicity (nada???)
• Chronic use increases the number of dopamine transporters: the very transporters it inhibits (not the production of, but activation.)
• Has less withdrawal than Adderall, since it suppresses c-Fos less.
• Chronic treatment increases glutamate levels in cerebrospinal fluid and impairs glutamatergic homeostasis in prefrontal cortex (in juvenile rats.)
  • http://raypeat.com/articles/articles/rosacea-inflammation-aging.shtml
• https://www.youtube.com/watch?v=EIgISomLl1o
  • Long-term treatment can lead to reduction in efficacy of the substance.
  • And discontinuation of use can lead to exacerbation of ADHD symptoms and chronic depression.
• Methylphenidate Exposure Induces Dopamine Neuron Loss and Activation of Microglia in the Basal Ganglia of Mice
• Methylphenidate and μ opioid receptor interactions: A pharmacological target for prevention of stimulant abuse
  • supra-therapeutic doses of MPH produce rewarding effects (surrogate measure for addiction in humans) in a conditioned place preference paradigm and upregulate μ-Opioid Receptor activity in the Striatum and nucleus accumbens, brain regions associated with reward circuitry
    • This requires activation of D1, but not D2.

IPPH (Isopropylphenidate) #

• Noradrenaline and Dopamine reuptake inhibitor. Has a much greater affinity for DAT than NET.
• Similar cognitive effects to ritalin, but less euphoria.
• Potentially increased heart rate, blood pressure, dry mouth, anxiety. Fairly relaxed with minimal sweating, possible vasoconstriction, jaw tension, and appetite suppression less significant than amph/ritalin.
• Alex Chen says it’s even better than focalin.
• Pretty hard to source

4F-MPH #

• Long as shit half life for some people. More euphoric; possibly a DRA.

Supplementation #

8 hour duration of action. 5-20mg orally.