39 replies to this topic

[phil8462643]

when its time, I will be in too!

[Reformed-Redan]

when its time, I will be in too!

Awesome. Will let you know. Checking prices around. Might take a while to get this one together with everything else that is going on.

[Babychris]

seriously guy's you're ready to pay more than 10/dose ? That's incredible

[Reformed-Redan]

seriously guy's you're ready to pay more than 10/dose ? That's incredible

That's an old price. And I don't think going with Ciproxifan is worth it.

[chris106]

Though depending on the time it takes of, I would definetely like to join the Pitolisant group-buy!
That and BPAP sound most interesting! Everything that promises to help with wakefullness and ADD symptoms I'm eager to try!

[meatsauce]

Hlaf life is 5 hours and the best dose is I think 80 mg.

Don;t know about you guys; but, I;m just being interested in being fully in the moment. Reading a book and understanding word for word.

Do you meditate yadayada? If we want to be fully in the moment (thats my goal too) we need to strengthen our perception and the amount of time we can hold attention. Meditation is the ultimate tool for this.

[Isochroma]

Waste of money. Tolerance. There's a better agent that does not produce tolerance.

Failproxifan

A-304121

Evidence for tolerance following repeated dosing in rats with ciproxifan, but not with A-304121

Blockade of presynaptic histamine H(3) receptors with potent and selective ligands improves cognitive function in rodents and there is significant interest in developing such drugs for long-term symptomatic treatment of CNS disorders such as attention deficit hyperactivity disorder (ADHD). Unfortunately, little is known about the effects of repeated exposure to H(3) receptor antagonists/inverse agonists.

We therefore investigated the effects of acute and repeated daily administration of two potent, brain penetrating H(3) receptor antagonists/inverse agonists, ciproxifan and A-304121, on rat body weight, food and water intake, core temperature and locomotor activity, as well as H(3) receptor density and gene expression levels.

Methylphenidate, used clinically for the treatment of ADHD, was included as an additional comparator. Ciproxifan, an imidazole-based compound, decreased food intake over the first 10 days and locomotor activity acutely, but these effects were lost after further repeated administration. The ex vivo binding studies revealed increased H(3) receptor density in rats following repeated administration of ciproxifan for 10 or 15 days; however, H(3) receptor gene expression was not changed.

In contrast, rats treated with the non-imidazole, A-304121, did not differ from controls on any measure during the observation period, while rats treated with methylphenidate exhibited hyperthermia and hyperactivity. The implications for potential long-term treatment with H(3) receptor antagonists in CNS disorders such as ADHD are discussed.

Further reading: Two Novel and Selective Nonimidazole H3 Receptor Antagonists A-304121 and A-317920 - II. In Vivo Behavioral and Neurophysiological Characterization [Free Full PDF]

Edited by Isochroma-Reborn, 27 November 2013 - 02:32 AM.

[Isochroma]

Histamine

Imidazole

The imidazole group is shared between Ciproxifan and Histamine but is not part of A-304121's structure. This imidazole group is required to activate the neural retrocompensative machinery which produces tolerance. Ciproxifan's imidazole group makes it 'similar enough' to Histamine to cause tolerance.

Edited by Isochroma-Reborn, 27 November 2013 - 03:03 AM.

[Isochroma]

From: Two Novel and Selective Nonimidazole H3 Receptor Antagonists A-304121 and A-317920 - II. In Vivo Behavioral and Neurophysiological Characterization [Free Full PDF]

"Taken together, the present studies confirm an imporant role for H3Rs in regulating cognition. Furthermore, they identify two novel, non-imidazole piperazine amides [Editor's Note: A-304121, A-317920] with functional antagonist activity at central H3Rs and cognition-enhancing activity at doses well below those inducing adverse effects in locomotor and general observation tests, thus providing overall superior therapeutic ratios when compared with thioperamide, ciproxifan, and T-2331."

Edited by Isochroma-Reborn, 27 November 2013 - 03:14 AM.

[Isochroma]

Further Reading: CEP-26401 (Irdabisant), a Potent and Selective Histamine H₃ Receptor Antagonist/Inverse Agonist with Cognition-Enhancing and Wake-Promoting Activities [Free Full PDF]