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Research Article Free access | 10.1172/JCI115955

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

I Gozes and M Fridkin

Department of Chemical Pathology, Sackler School of Medicine, Tel Aviv University, Israel.

Find articles by Gozes, I. in: JCI | PubMed | Google Scholar

Department of Chemical Pathology, Sackler School of Medicine, Tel Aviv University, Israel.

Find articles by Fridkin, M. in: JCI | PubMed | Google Scholar

Published September 1, 1992 - More info

Published in Volume 90, Issue 3 on September 1, 1992
J Clin Invest. 1992;90(3):810–814. https://doi.org/10.1172/JCI115955.
© 1992 The American Society for Clinical Investigation
Published September 1, 1992 - Version history
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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 greater than or equal to 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.

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