P-21 is a heavily modified peptide nootropic that was originally designed from CNTF antibodies, not Cerebrolysin, as is commonly thought. Cerebrolysin was the motivation to research CNTF antibodies, as it was shown to be responsible for its neurogenesis elements.
The ambition with the P21 nootropic drug was to "incorporate new neurons into already existing neural networks", to battle the crippling disease called Alzheimer's. Despite the ongoing and continual research behind P-21, there exist no clinical trials.
The central role of p21 in sensing and responding to a plethora of stimuli
p21 responds to a variety of stimuli to promote growth-inhibitory activities that depend primarily on its ability to inhibit the kinase activity of cyclin-dependent kinase 2 (CDK2). p21-induced cell cycle arrest also depends on its ability to inhibit CDK1. p21 can inhibit cellular proliferation independent of CDK2 inhibition by inhibiting proliferating cell nuclear antigen (PCNA), which is required for S phase progression. Some of the anti-proliferative activities of p21 rely on its multiple protein–protein interactions and its ability to regulate gene transcription. The various physiological responses triggered by p21 are interconnected. For example, cell cycle arrest induced by p21 promotes DNA repair by allowing sufficient time for the damaged DNA to be repaired before it is passed to daughter cells and is a major route by which p21 exerts its anti-apoptotic activities. Similarly, the ability of p21 to regulate gene expression is important in promoting cellular senescence. The effect of p21 on gene transcription is generally inhibitory, but p21 can also activate gene transcription under certain conditions. The role of p21 in promoting DNA damage-induced and p53-dependent cell cycle arrest is well established and not the focus of this Review, and its role in mediating cellular responses to oxidative stress is well described188.
The dosage in the rat studies is varied, with some studies using the original peptide 6 11-mer at 10x the dose of other research papers. It's a bit of a mess, but we shall narrow it down and just observe P021 dosages, which still is hugely variable.
In one study 289 mcg per kg of rat weight was used. Rats have a dividing number of 6.3, meaning that for a 65 kg human, 2981 mcg per day was given.
However, this was given via oral administration, which means if you are taking it intranasally, or subcutaneously, the dosage should be lower.
"We administered P021 by gavage, 500 nmol (289.15 μg)/kg body weight daily for 3 months"
Numerous studies use oral administration, via incorporation of P021 into the feed of the rats, meaning their dosage depended on the amount they ate! How inaccurate!
The weight also wasn't recorded. This link shows the weight of the corresponding rats and shows that females at 3 months should weigh approximately 20 grams. Meaning, multiply by 50 for the per/kg amount, divide by 6.3 that's the human per kg dose. Nearly 50 mg oral!
"consumed ∼2.7 g diet/day which amounted to 60 nmoles x 2.7 = 162 nmoles P021/mouse/day" = 0.0936 mg per mouse per day. Multiply by 50 to get the kilogram amount, divide by 12 because they're mice [R], and finally multiply by 65 to get 25.35 mg per day. This was given orally, remember!
"P021 is able to cross the blood-brain barrier to exert its neurogenic/neurotrophic activities, has a plasma half-life of >3 h, is 100% stable in intestinal fluid during 2 h, 90 and >90% stable in gastric juice during 30 min"
P21 is a very short peptide, and 3 mg is highly potent considering this fact.