Beneficial effects of PKF275-055, a novel, selective, orally bioavailable, long-acting dipeptidyl peptidase IV inhibitor in streptozotocin-induced diabetic peripheral neuropathy

Roberto Bianchi, I. Cervellini, C. Porretta-Serapiglia, N. Oggioni, B. Burkey, P. Ghezzi, G. Cavaletti, G. Lauria

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

1-[(2-adamantyl)amino]acetyl-2-cyano-(S)-pyrrolidine, monohydrochloride (PKF275-055), a vildagliptin analog, is a novel, selective, potent, orally bioavailable, and long-acting dipeptidyl peptidase IV inhibitor. We studied the effect of PKF275-055 administration on the prevention, protection, and treatment of diabetic neuropathy in the streptozotocin-induced diabetic rat. PKF275-055 improved body and muscle weight. Oral glucose tolerance tests showed a marked improvement in glucose metabolism under all treatment schedules. When tested in prevention and protection experiments, PKF275-055 completely averted the decrease of Na +/K +-ATPase activity and partially counteracted the nerve conduction velocity (NCV) deficit observed in untreated diabetic rats but had no effects on abnormal mechanical and thermal sensitivity. When used in a therapeutic setting, PKF275- 055 induced a significant correction in the alteration in Na +,K +- ATPase activity and NCV present in untreated diabetics. Diabetic rats developed mechanical hyperalgesia within 2 weeks after streptozotocin injection and exhibited significantly longer thermal response latencies. It is noteworthy that PKF275-055 treatment restored mechanical sensitivity thresholds by approximately 50% (p <0.01) and progressively improved the alteration in thermal responsiveness. In conclusion, PKF275-055 showed an anabolic effect, improved oral glucose tolerance, and counteracted the alterations in Na +,K +-ATPase activity, NCV, and nociceptive thresholds in diabetic rats. The present data support a potential therapeutic effect of PKF275-055 in the treatment of rodent diabetic neuropathy.

Original languageEnglish
Pages (from-to)64-72
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume340
Issue number1
DOIs
Publication statusPublished - Jan 2012

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Dipeptidyl-Peptidase IV Inhibitors
Diabetic Neuropathies
Peripheral Nervous System Diseases
Streptozocin
Neural Conduction
Hot Temperature
Glucose Tolerance Test
Therapeutics
monohydrochloride 1-((2-adamantyl)amino)acetyl-2-cyano-(S)-pyrrolidine
Anabolic Agents
Hyperalgesia
Therapeutic Uses
Reaction Time
Rodentia
Appointments and Schedules
Body Weight
Glucose
Muscles

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Beneficial effects of PKF275-055, a novel, selective, orally bioavailable, long-acting dipeptidyl peptidase IV inhibitor in streptozotocin-induced diabetic peripheral neuropathy. / Bianchi, Roberto; Cervellini, I.; Porretta-Serapiglia, C.; Oggioni, N.; Burkey, B.; Ghezzi, P.; Cavaletti, G.; Lauria, G.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 340, No. 1, 01.2012, p. 64-72.

Research output: Contribution to journalArticle

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