δ opioid receptor agonists(δ-opioid receptor agonists), κ opioid receptor agonists(Kappa opioid receptor agonists), μ opioid receptor agonists(Mu opioid receptor agonists)

Therapeutic Areas

Nervous System Diseases

Active Indication

Pain

Inactive Indication-

Originator Organization

Phoenix Biotechnology, Inc.

Active Organization

Phoenix Biotechnology, Inc.

Inactive Organization

Phoenix PharmaLabs, Inc.

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

100 Clinical Results associated with PPL-103

100 Translational Medicine associated with PPL-103

100 Patents (Medical) associated with PPL-103

Literatures (Medical) associated with PPL-103

01 Dec 2022·Progress in Neuro-Psychopharmacology and Biological Psychiatry

PPL-103: A mixed opioid partial agonist with desirable anti-cocaine properties

Article

Author: Toll, Lawrence ; Cippitelli, Andrea ; Zribi, Gilles

Cocaine use disorder (CUD) is a persistent public health problem for which no effective medications are available. PPL-103 is an opioid receptor ligand with partial agonist activity at mu, kappa and delta opioid receptors, with a greater efficacy for kappa and low efficacy at mu receptors. Because chronic cocaine use induces changes in the kappa opioid receptor/dynorphin system, we hypothesized that a kappa partial agonist, such as PPL-103, would attenuate the aversive properties of the upregulated kappa system, resulting in effective treatment approach for CUD. We tested the effects of PPL-103 on cocaine self-administration models that recapitulate core aspects of CUD in humans. We found that PPL-103 reduced both long and short access cocaine self-administration, motivation to respond for cocaine, and binge-like cocaine taking, in rats. Operant responding for food, fentanyl and locomotor behavior were not altered at doses that decreased cocaine infusions. Repeated PPL-103 treatment did not lead to tolerance development. PPL-103 also reduced both priming- and cue-induced reinstatement of cocaine seeking, being more effective in the former. Surprisingly, PPL-103 reduced self-administration parameters and reinstatement in rats previously treated with the long-acting kappa receptor antagonist JDTic more potently than in non-JDTic treated animals, whereas naltrexone injected to rats subsequent to JDTic administration increased self-administration, suggesting that the partial mu agonist activity, rather than kappa agonism is important for reduction in cocaine taking and seeking. However, partial kappa activation seems to increase safety by limiting dysphoria, tolerance and addiction development. PPL-103 displays a desirable profile as a possible CUD pharmacotherapy.

Frontiers in PsychiatryQ3 · MEDICINE

In Vitro and In Vivo Profile of PPL-101 and PPL-103: Mixed Opioid Partial Agonist Analgesics with Low Abuse Potential

Q3 · MEDICINE

ArticleOA

Author: Toll, Nicholas ; Lawson, John A ; Khroyan, Taline V ; Polgar, Willma E ; Toll, Lawrence ; Crossman, William ; Cippitelli, Andrea

Opiates are still the most effective and widely used treatments for acute and chronic pain. However, the problems associated with morphine and other standard opioid analgesics severely limit their effectiveness in the clinic. PPL-101 and PPL-103 derived from morphine and morphinan ring systems contain a chiral N-substituent, which confers it with a unique combination of high-binding affinities and partial agonist activities at mu, delta, and kappa opioid receptors, leading to unique in vivo pharmacology compared to other conventional opioids. Acute antinociceptive and reward acquisition of PPL-101 and PPL-103 were assessed in mice using the tail flick assay and conditioned place preference (CPP) paradigm, respectively. The reinforcing effects of these compounds were assessed in rats using the self-administration paradigm. In mice, PPL-101 and PPL-103 produced antinociception reaching maximal effects that were equivalent to morphine at approximately 1/3 and 1/10 of morphine's dose, respectively. PPL-101-induced antinociception was attenuated following pretreatment with the kappa antagonist JDTic, but not the mu opioid antagonist beta-FNA. In mice, PPL-101 and PPL-103 produced dose-dependent decreases in activity, similar to other kappa agonists; however, they did not produce conditioned place aversion, and in fact elicited a trend toward CPP. In rats, neither PPL-101 nor PPL-103 were self-administered when substituted for morphine and PPL-101 attenuated morphine self-administration, when administered systemically prior to the self-administration session. Collectively, these results indicate that mixed opioid receptor partial agonists can produce potent antinociceptive activity with a lack of aversion in mice and without being self-administered in rats. Compounds with this profile could be superior analgesics with greatly reduced addiction liability and fewer side-effects compared to traditional opiates.

100 Deals associated with PPL-103

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Indication	Highest Phase	Country/Location	Organization	Date
Pain	Preclinical	-	Phoenix Biotechnology, Inc.	-

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