RPEP-00093 · 1988Three opioid peptide families showed distinct, non-overlapping distributions in the preoptic brain region.
Beta-endorphin fibers were mainly in the periventricular nucleus. Dynorphin B fibers were more uniformly distributed with few cell bodies. Enkephalin (peptide E) had hundreds of cell bodies, concentrated in specific nuclei.
The key sexual dimorphism: male rats had significantly more enkephalin cells in the anteroventral periventricular nucleus (AVPv) than females. This was despite the AVPv being physically larger in female rats.
This sex difference was at least partially dependent on perinatal gonadal steroids. Early hormone exposure during the critical developmental window permanently organized the number of enkephalin cells, a process called organizational hormone effects.
No sex difference was found in enkephalin cells in the anterodorsal preoptic nucleus, showing the dimorphism was region-specific, not a general property of enkephalin neurons.
Simerly, R B; McCall, L D; Watson, S J · Animal Study
RPEP-00345 · 1995Beta-endorphin in the MPOA dose-dependently impaired male rat sexual behavior, prevented by naloxone, while other opioid peptides were less effective at equivalent doses.
van Furth, W R; van Emst, M G; van Ree, J M · Animal Study
RPEP-00849 · 2003PT-141 (bremelanotide) induced sexual arousal in both male and female animals through central MC3R/MC4R activation, representing a mechanistically novel approach to sexual dysfunction treatment through brain desire pathways rather than peripheral blood flow.
Molinoff, P B; Shadiack, A M; Earle, D; Diamond, L E; Quon, C Y · Animal Study
RPEP-00903 · 2004Intranasal PT-141 induced dose-dependent erectile responses in both healthy men and Viagra-responsive ED patients in a double-blind, placebo-controlled trial, with rapid onset and acceptable safety — validating intranasal melanocortin ED therapy.
Diamond, L E; Earle, D C; Rosen, R C; Willett, M S; Molinoff, P B · RCT
RPEP-00924 · 2004PT-141 intranasal demonstrated ED treatment efficacy in clinical trials through central melanocortin receptor activation, with development progressing toward potential approval as a first-in-class brain-acting sexual dysfunction therapy.
Hedlund, Petter · Review
RPEP-00959 · 2004PT-141 (melanocortin agonist) selectively increased sexual solicitation (proceptive) behavior in female rats without affecting locomotion or other behaviors — demonstrating specific melanocortin modulation of female sexual desire/motivation.
Pfaus, James G; Shadiack, Annette; Van Soest, Tanya; Tse, Maric; Molinoff, Perry · Animal Study
RPEP-00969 · 2004SC PT-141 induced dose-dependent erectile responses in ED patients (double-blind, placebo-controlled) with characterized pharmacokinetics, acceptable safety, and practical SC delivery — advancing toward clinical approval.
Rosen, R C; Diamond, L E; Earle, D C; Shadiack, A M; Molinoff, P B · RCT
RPEP-01028 · 2005Co-administration of low-dose intranasal PT-141 (melanocortin agonist) with sildenafil (PDE5 inhibitor) produced synergistic erectile responses in ED patients — combining central desire/arousal with peripheral vasodilation for superior outcomes.
Diamond, L E; Earle, D C; Garcia, W D; Spana, C · RCT
RPEP-01105 · 2005Antimicrobial peptides with dual spermicidal and microbicidal properties could serve as vaginal microbicide contraceptives — simultaneously preventing STIs (HIV, HSV, gonorrhea) and pregnancy through a single peptide-based topical product.
Yedery, R D; Reddy, K V R · Review
RPEP-01128 · 2006Intranasal bremelanotide (PT-141) significantly increased subjective sexual arousal, desire, and genital sensation in premenopausal women with sexual arousal disorder in a double-blind, placebo-controlled RCT — landmark evidence leading toward FDA approval for female sexual dysfunction.
Diamond, Lisa E; Earle, Dennis C; Heiman, Julia R; Rosen, Raymond C; Perelman, Michael A; Harning, Ronald · RCT
RPEP-01279 · 2007Bremelanotide activates female sexual function through MC3R/MC4R in hypothalamic/limbic sexual circuits, enhancing desire and arousal through dopaminergic and oxytocinergic pathway modulation — the comprehensive CNS mechanism supporting its clinical development for female HSDD.
Pfaus, James; Giuliano, François; Gelez, Hélène · Review
RPEP-01288 · 2007Melanocortin agonists (bremelanotide, melanotan II) treat sexual dysfunction in both sexes through central MC3R/MC4R activation: ED in men and HSDD/FSAD in women — the only drug class targeting desire/arousal centrally for both genders.
Shadiack, Annette M; Sharma, Shubh D; Earle, Dennis C; Spana, Carl; Hallam, Trevor J · Review
RPEP-01413 · 2008SC bremelanotide significantly improved erectile responses in sildenafil-failure ED patients in a double-blind, placebo-controlled RCT — demonstrating melanocortin central mechanism (desire/arousal) rescues patients where PDE5 peripheral mechanism (blood flow) fails.
Safarinejad, Mohammad Reza; Hosseini, Seyyed Yousof · RCT
RPEP-04980 · 2020Vaginal AMPs (defensins, LL-37, lactoferrin, SLPI, calprotectin, lysozyme, elafin) provide innate defense against STIs; some (LL-37, magainin 2, nisin) have dual spermicidal-antimicrobial activity.
Madanchi, H; Shoushtari, M; Kashani, H H; Sardari, S · Review
RPEP-04991 · 2020Bremelanotide significantly improved desire and reduced HSDD-related distress in Phase 2/3 trials, with nausea (39.9%), flushing (20.4%), and headache (11%) as main side effects.
Mayer, Danielle; Lynch, Sarah E · Review
RPEP-05507 · 2021From 242 exit surveys and 80 telephone interviews, bremelanotide-treated women described increased sexual desire, physical arousal, and improved sexual activity quality — physiological responses not reported by placebo-treated women, who described non-physiological benefits only.
Koochaki, Patricia; Revicki, Dennis; Wilson, Hilary; Pokrzywinski, Robin; Jordan, Robert; Lucas, Johna; Williams, Laura A; Sadiq, Amama; Krop, Julie · Rct