A fatty neuropeptide: Potential drug for noninvasive impotence treatment in a rat model

I. Gozes*, M. Fridkin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Vasoactive intestinal peptide (VIP), a key penile neurotransmitter, induces erection after local injection in man. To augment the therapeutic potential of VIP for impotence treatment and circumvent difficulties of direct penile injections, a strategy was designed to increase peptide hydrophobicity. This was accomplished by the synthesis of a conjugate of VIP and stearic acid (stearyl-VIP). Upon penile topical application, stearyl-VIP, in contrast to native VIP, significantly increased sexual function as measured by copulatory activity and penile reflexes (erections) in testosterone-treated, castrated rats. In addition, stearyl-VIP penetrated the body in amounts severalfold greater than VIP. Pharmacokinetic studies demonstrated 10-fold higher penile concentrations of stearyl-VIP, as compared with that measured in the blood 15 min after application, with a gradual decrease thereafter. The peak of incorporation into peripheral tissues that was observed 30 min after administration was 1,000-fold less than that found in the penile tissue. Tissue extraction and Chromatographic analysis revealed that stearyl-VIP remained essentially intact for ≥ 15 min and was cleared after 1 h. Thus, topically administered stearyl-VIP had increased bioavailability in comparison with VIP without apparent toxicity, suggesting significant therapeutic potential.

Original languageEnglish
Pages (from-to)810-814
Number of pages5
JournalJournal of Clinical Investigation
Volume90
Issue number3
StatePublished - 1992

Keywords

  • Lipophilic peptides
  • Penile reflexes
  • Sexual behavior
  • Vasoactive intestinal peptide

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