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The neurobiology of bremelanotide for the treatment of hypoactive sexual desire disorder in premenopausal women

Published online by Cambridge University Press:  18 January 2021

James G. Pfaus ,
Amama Sadiq ,
Carl Spana  and
Anita H. Clayton
James G. Pfaus
Affiliation:
Centro de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa, Veracruz, Mexico
Amama Sadiq*
Affiliation:
AMAG Pharmaceuticals, Inc., Waltham, Massachusetts, USA
Carl Spana
Affiliation:
Palatin Technologies, Inc., Cranbury, New Jersey, USA
Anita H. Clayton
Affiliation:
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, Virginia, USA
*
*Author for correspondence: Amama Sadiq, MD, MPH Email: asadiqmd@gmail.com
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Abstract

Hypoactive sexual desire disorder (HSDD) is a common female sexual dysfunction and is estimated to affect approximately 10% of women in the United States. It has been suggested that HSDD is associated with an imbalance of hormone and neurotransmitter levels in the brain, resulting in decreased excitation, increased inhibition, or a combination of both. Evidence suggests neurotransmitters, including dopamine (DA), norepinephrine, and serotonin, as well as hormones such as estradiol and testosterone, contribute to female sexual desire and response. Current treatments for HSDD include psychotherapy, and two US Food and Drug Administration-approved medications for premenopausal women: flibanserin, a serotonin mixed agonist and antagonist, and bremelanotide, a melanocortin receptor (MCR) agonist. Melanocortins are endogenous neuropeptides associated with the excitatory pathway of the female sexual response system. MCRs are found throughout the body, including the brain. Bremelanotide is an MCR agonist that nonselectively activates several of the receptor subtypes, of which subtype 4 (MC4R) is the most relevant at therapeutic doses. MC4R is predominantly expressed in the medial preoptic area (mPOA) of the hypothalamus in the brain, and is important for female sexual function. Animal studies suggest that bremelanotide may affect female sexual desire by activating presynaptic MC4Rs on neurons in the mPOA of the hypothalamus, leading to increased release of DA, an excitatory neurotransmitter that increases sexual desire. This review presents what is known about the mechanism of action of bremelanotide in the context of treating HSDD.

Keywords

DopamineGABAhypoactive sexual desire disordermelanocortin receptor agonistnorepinephrineserotonin
Type
Review
Information
CNS Spectrums , Volume 27 , Issue 3 , June 2022 , pp. 281 - 289
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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