A WORD OF CAUTION ON BREMELANOTIDE (PT-141)

In his role as a drug policy analyst, Leonard wishes to issue the following advisory on the possible abuse potential of bremelanotide (PT-141):

Posted April 18, 2006


1.) PT-141, recently named bremelanotide by international convention, is being developed as a treatment for erectile dysfunction (ED) and female sexual dysfunction (FSD) by Palatin Technologies, Inc. of New Jersey.

2.) Bremelanotide significantly promotes solicitational behavior in female rats, and appears to be the first true aphrodesiac. (See J. Pfaus et al., "Selective Facilitation of Sexual Solicitation in the Female Rat by a Melanocortin Agonist")    

3.) In humans, bremelanotide produces an "enjoyable arousal response" and induces sexual desire within 10-20 minutes after intranasal administration, with the effects of bremelanotide continuing past orgasm.

4.) The effects of bremelanotide are in contrast to phosphodiesterase inhibitors such as Viagra, Levitra and Cialis, which do not induce subjective erotogenic effects in the absence of sexual stimulation.

5.) A 1998 patent for MTII, a less potent form of bremelanotide, described its effect across a wide range of mammals. In U.S. Patent  #6,051,555, "Stimulating Sexual Response in Females," the inventor suggested that this similar erotogenic peptide "may be administered to increase the libido of female animals in captivity [] to make them more receptive to coitus, in addition to providing male animals with increased libido [] the peptides may be administered to stallions which, for psychological and/or physical reasons will not mount a (mock) female phantom used in the collection of sperm." (See M. Hadley, "Discovery that a Melanocortin Regulates Sexual Functions in Male and Female Animals.")

6.) According to the 2003  U.S. Patent #6,579,968, bremelanotide (described therein as "Compound 1") is approximately 50 times the potency of MTII, and the effects are dose-dependent. The therapeutic window between the dose necessary for the "desired effect" and the dose that produces adverse effects such as yawning and stretching or nausea is "1000-fold", permitting multiple doses of bremelantotide to be administered. (See C. Blood et al., "Compositions and Methods for Treatment of Sexual Dysfunctions," assigned to Palatin Technologies, Inc.)

7.) The patent indicates that bremelanotide is preferably administered by inhalation, but may be applied by any method permitting it to cross an epidermal layer, including injection, topical application, and orally in sufficient dosages or in the presence of a penetrating agent for peptides.

8.) Carl Spana, PhD, CEO of Palatin Technologies, Inc. has been quoted as stating that bremelanotide aroused female rodents "so quickly they started mounting males" and that it may "easily" be made into an oral form. (See article from Observer: By Robin McKie, science editor)

9.) Currently, about 400 men and less than 100 women volunteers subjects have been exposed to bremelanotide in Phase 1 and 2 clinical trials and in "at-home" settings.

10.) It is the intention of Palatin Technologies, Inc. and King Pharmaceuticals, Inc. to distribute bremelanotide worldwide.

11.) Distribution of bremelanotide may parallel the epidemiology of Viagra (sildenafil), resulting in wide-spread casual use by non-patient populations, international availability without physician evaluations, counterfeiting, and clandestine manufacture.

12.) The marketing of bremelanotide will be similar to that of Viagra, including frequent full-page newpaper and television advertisements, resulting in a secondary  "grey-market" with bremelanotide avalable from numerous internet sources in the absence of medical diagnoses.

13.) However, in contrast to the relatively non-problematic non-medical use of Viagra, the subjective erotogenic qualities of bremelanotide may ultimately pose a hazard to the public health.

14.) Bremelanotide appears to possess the liido-enhancing properties of cocaine and methamphetamine, but without the central stimulating effect of these substances.

15.) While recognizing that bremelanotide may be effective in ameliorating clearly-defined instances of FSD or ED and may be successfully employed as a marital adjuct, global distribution of an erotogenic drug that selectively induces sexual response may also result in signifiant societal problems, viz.:

a.) unanticipated social consequences from non-medical use.
b.) substantially heightened promiscuity across age groups and genders.
c.) surreptitious administration to unwitting individuals, resulting in drug-induced consensual sexual activity among individuals that would not consent in the absence of the drug.
d.) a increase in "date-rape" in conjuction with flunitrazepam or other drugs.
e.) an increase in the incidence of prostitution, including the drug's employment in human trafficking.
f.) an increase in sexual crimes, including rape, gang-rape, and child abuse.
g.) uncontrolled use among minors.
h.) abuse among users of crack cocaine, cocaine, or methamphetamine.
i.) abuse among populations that would not normally employ any unprescribed drug.
j.) overdose scenarios requiring medical intervention.
k.) medical complications from acute or chronic use.
l.) an increase in sexual aberrrations that are rarely seen by clinicians.
m.) increased incidence of AIDS and other sexually transmitted diseases.
n.) increased incidence of unwanted births, and among lower age cohorts.
o.) the advent of criminal organizations specializing in manufacture or distribution of this or related substances.

16.) Compounding the possible threat potential are two factors: a.) bremelantotide is an easily synthesized peptide that may be manufactured by numerous means known to the art - including table-top automated procedures - and from relatively inexpensive and ubiquitous precursors; and b.) while easily produced, the dosage range employed in clinical trials is also modest, ranging from 10-20 mgs. Thus, each kilogram of bremelanotide contains 50,000-100,000 dosage units, facilitating its transport or smuggling.

17.) Currently, the results of clinical trials on bremelanotide are reported to the FDA by the drug developer, Palatin Technologies, Inc. Self-reporting of clinical trials may be subject to inherent bias, e.g. as observed in the case of Vioxx and other drugs.

18.) It may be noted that of the more than 400 controlled substances, almost all are products products of efforts by the pharmaceutical industry to develop effective medicines.

19.) However, some researchers have proposed that the underlying disorders providing the rationale for developing bremelanotide, e.g. female sexual dysfunction (FSD), may be in some instances constructs of the pharmaceutical industry.

20.) Nevertheless, it is asserted that current FDA protocols may be inadequate to provide early warning of the breadth of an imminent hazard to the public health posed by new cognitive agents, in this case those affecting libido.

21.) It is suggested that FDA discontinue clinical trials of bremelanotide until public hearings are conducted on the potential abuse liability of this and related compounds by regulatory agencies, including FDA, HHS, DOJ, and the Commission on Bioethics.

22.) It is further asserted that, in the event bremelanotide is not approved by FDA, bremelanotide and related agonists may continue to pose a hazard due to off-patent international manufacture and distribution.

23.) Federal agencies are encouraged to make early inquiry among volunteers in existing bremelanotide clinical trials and among independent users to properly assess the range of use or abuse that may occur. Such inquiry should include assessment of the increasing internet interest in off-patent availability of bremelanotide and similar melanocortin agonists.

25.) It is proposed that - at the inception of any effort at drug design of cognitive agents by industry - independent reviews be conducted on the possible social liabilty of a compound affecting primary human emotions.

26.) It is further proposed that a policy advisory group be established to continually identify novel cognitive agents under development by the pharmaceutical and biotech industries, in an effort to anticipate the social impact of such agents.

Researchers, volunteer subjects, independent users of bremelanotide,and concerned individuals and organizations are encouraged to comment on this advisory to bremelanotide@freepickard.org

New Developments

1.) To:bremelanotide@freepickard.org Date: Sun, 25 Jun 2006
An individual recently blogged that the Postal Service seized the bremelanotide
he had ordered from overseas. (click here for "Notice of FDA Action") *link to* the message below:

Notice of FDA Action

A mail shipment addressed to you from a foreign country is being held
by
the post office at the request of the U.S. Food and Drug
Administration.

Product Description: 250mg Bremelanotide powder in 4.5cmx1cm (Height x
Diameter) clear plastic vial with red screw cap.

DETAINED 06-01-2006

The following products are subject to refusal of admission into the
United States under authority of the Federal Food Drug and Cosmetic Act
(FD&CA), Public Health Service Act(PHSA), or other related acts in that
they appear to violate as indicated below:

505(a), 801(a)(3); Unapproved

The article appears to be a new drug without an approved new drug
application.

This Notice does not in any manner accuse you of violating the Law.

L.W.L. (name withheld),
Compliance Officer
U.S. Food and Drug Administration