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Buprenorphine (CAS: 52485-79-7)

Partial mu opioid receptor agonist

NanoBUP™ Oral Swallowed Capsule - Phase 2a clinical program

 

NanoBUP™, an innovative formulation that provides easy-to-take swallowed capsule dosage form, represents a breakthrough in buprenorphine delivery as a replacement for sublingual buprenorphine. Currently, oral buprenorphine is available as sublingual tablets, films, and buccal patches. NanoBUP™ oral swallowed buprenorphine capsule, initially developed under a NIDA SBIR contract, has been shown in multiple clinical studies to produce similar bioavailability with a lower Cmax compared to sublingual buprenorphine, which may promote less craving and improve weaning during maintenance therapy. In addition, it may have lesser addiction risk compared to sublingual buprenorphine formulation. Although, organizations like SAMHSA, NIDA, and the World Health Organization agree that medication-assisted treatment decreases opioid use, opioid related-deaths, and increases success in treatment, only approximately one-third of patients have been found to easily access it. One way to increase availability is to create easier and more tolerable dosing options, such as NanoBUP™ oral swallowed capsule. NanoBUP™ oral swallowed buprenorphine capsule has bee tested in three Phase 1 clinical studies and one Phase 2a clinical study.


 
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PRX-3140 (CAS: 869493-26-5)

5-HT4 Selective Agonist

Oral Capsule - Phase 2a clinical program

PRX-3140, an orally-bioavailable 5-HT4 selective agonist, has completed five Phase 1 and 2 clinical studies. PRX-3140 stimulates cognition and memory by selectively activating the 5-HT4 G-protein coupled receptor in the brain to produce and release acetylcholine, a neurotransmitter that plays a role in learning and memory. As Alzheimer's disease progresses, acetylcholine production declines, and brain levels of this critical neurotransmitter decline also. PRX-3140 has the potential to slow the progression of the disease with fewer and less severe side effects than current Alzheimer drugs. A randomized, double-blind, placebo-controlled Phase 2a clinical trial was completed to assess the effects of PRX-3140 following two weeks of treatment as monotherapy and separately in combination with donepezil (Aricept®) in patients with mild Alzheimer's disease. PRX-3140 appeared to be well tolerated alone and in combination with Aricept® with no serious drug-related adverse events. In October, 2009, the FDA approved a Physician-Sponsored IND and continuation of the fourth six-month open label extension of PRX-3140.


NP-18-2 is a proprietary oral small molecule 5-HT2b antagonist for potential treatment of pulmonary arterial hypertension (PAH) and related disorders. PAH is characterized by the elevation of pulmonary vascular pressures with progressive vascular hyperplasia and narrowing of the blood vessels of the lungs, ultimately leading to right-sided heart failure. Recently, several studies have suggested a role for serotonin 5-HT in the etiology and progression of PAH. Isolated smooth muscle and endothelial cells from pulmonary arteries express mRNAs for several 5-HT receptors including 5-HT1B, 5-HT2A, 5-HT2B, and 5-HT7 receptors. 5-HT is a pulmonary vasoconstrictor and can also act as a growth amplification factor. Thus, by activating its cognate receptors, 5-HT has a dual effect on the pulmonary circulation, contributing to both vasoconstriction and vascular remodeling. NP-18-2 has been studied in over 100 healthy subjects in patients in Phase 1 and 2 studies.


NP-18-3 is a highly selective and potent agonist of the serotonin 5-HT1A receptor that was under development for the treatment of Major Depressive Disorder (MDD). The molecule, an amino butyl piperazine, is chemically distinct from the azapirone class to which most 5-HT1A agonists belong. Preclinical studies, such as the forced swim model in rodents, suggest anti-depressant activity. A total of 7 clinical studies have been conducted with NP-18-3 including four Phase I studies, two clinical trials in patients with generalized anxiety disorder (GAD), and one clinical trial in patients with MDD in which a total of 443 human subjects received the drug. There have been no drug-related serious adverse events (SAEs) and most adverse events were rated as mild to moderate by the investigators.