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Routes of administration | Subcutaneous injection |
Drug class | Melanocortin MC4 receptor agonist |
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PL-6983 is a synthetic peptide and selective MC4 receptor agonist which is under development by Palatin Technologies for the treatment of female sexual dysfunction and erectile dysfunction. [1] [2] It was developed as a successor to/replacement of bremelanotide (PT-141) due to concerns of the side effect of increased blood pressure seen with the latter in clinical trials. [1] [2] Relative to bremelanotide, PL-6983 produces significantly lower increases in blood pressure in animal models. [1] [2] The drug has reportedly been in pre-clinical development for all medical indications since 2008. [3] Palatin has stated that "We are focusing development efforts on bremelanotide for [female sexual dysfunction], but are continuing evaluation of PL-6983." [4] The chemical structure of PL-6983 has yet to be made public.
Sexual arousal disorder is characterized by a lack or absence of sexual fantasies and desire for sexual activity in a situation that would normally produce sexual arousal, or the inability to attain or maintain typical responses to sexual arousal. The disorder is found in the DSM-IV. The condition should not be confused with a sexual desire disorder.
Bremelanotide, sold under the brand name Vyleesi, is a medication used to treat low sexual desire in women. Specifically it is used for low sexual desire which occurs before menopause and is not due to medical problems, psychiatric problems, or problems within the relationship. It is given by an injection just under the skin of the thigh or abdomen.
Female sexual arousal disorder (FSAD) is a disorder characterized by a persistent or recurrent inability to attain sexual arousal or to maintain arousal until the completion of a sexual activity. The diagnosis can also refer to an inadequate lubrication-swelling response normally present during arousal and sexual activity. The condition should be distinguished from a general loss of interest in sexual activity and from other sexual dysfunctions, such as the orgasmic disorder (anorgasmia) and hypoactive sexual desire disorder, which is characterized as a lack or absence of sexual fantasies and desire for sexual activity for some period of time.
The melanocortins are a family of neuropeptide hormones which are the ligands of the melanocortin receptors. The melanocortin system consists of melanocortin receptors, ligands, and accessory proteins. The genes of the melanocortin system are found in chordates. Melanocortins were originally named so because their earliest known function was in melanogenesis. It is now known that the melanocortin system regulates diverse functions throughout the body, including inflammatory response, fibrosis, melanogenesis, steroidogenesis, energy homeostasis, sexual function, and exocrine gland function.
Melanotan II is a synthetic analogue of the peptide hormone α-melanocyte-stimulating hormone (α-MSH) that stimulates melanogenesis and increases sexual arousal.
Sex and drugs refers to the influence of substances on sexual function and experience. Sex and drugs date back to ancient humans and have been interlocked throughout human history. Sexual performance is known as the execution of the act of sex and the quality of sexual activity. This includes elements such as libido, sexual function, sensation . Drugs are termed as any chemical substance that produces a physiological and or psychological change in an organism. Drugs categorized as psychoactive drugs, antihypertensive drugs, antihistamines, cancer treatment, and hormone medication have a significant impact on sexual performance. Various drugs result in different effects, both positive and negative. Negative effects may include low libido, erection issues, vaginal dryness and anorgasmia. Positive effects usually address these issues, overall enhancing sexual performance and contributing to a more enjoyable sexual experience. It is crucial to know that the impact of drugs on sexual performance varies among individuals, especially among different genders.
A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin, a neurotransmitter and hormone and the endogenous ligand of the serotonin receptors.
Flibanserin, sold under the brand name Addyi, is a medication approved for the treatment of pre-menopausal women with hypoactive sexual desire disorder (HSDD). The medication improves sexual desire, increases the number of satisfying sexual events, and decreases the distress associated with low sexual desire. The most common side effects are dizziness, sleepiness, nausea, difficulty falling asleep or staying asleep and dry mouth.
The orexin receptor (also referred to as the hypocretin receptor) is a G-protein-coupled receptor that binds the neuropeptide orexin. There are two variants, OX1 and OX2, each encoded by a different gene (HCRTR1, HCRTR2).
Selective androgen receptor modulators (SARMs) are a class of drugs that selectively activate the androgen receptor in specific tissues, promoting muscle and bone growth while having less effect on male reproductive tissues like the prostate gland.
Melanocortin 4 receptor (MC4R) is a melanocortin receptor that in humans is encoded by the MC4R gene. It encodes the MC4R protein, a G protein-coupled receptor (GPCR) that binds α-melanocyte stimulating hormone (α-MSH). In mouse models, MC4 receptors have been found to be involved in feeding behaviour, the regulation of metabolism, sexual behaviour, and male erectile function.
THIQ is a drug used in scientific research, which is the first non-peptide agonist developed that is selective for the melanocortin receptor subtype MC4. In animal studies, THIQ stimulated sexual activity in rats, but with little effect on appetite or inflammation. This supports possible application of MC4 selective agonists for the treatment of sexual dysfunction in humans, although THIQ itself has poor oral bioavailability and a short duration of action so improved analogues will need to be developed.
PF-219,061 is a drug that was under development by Pfizer which acts as a potent and highly selective agonist for the dopamine D3 receptor. It was under development as a potential medication for the treatment of female sexual dysfunction. It did not advance into clinical trials.
Vortioxetine, sold under the brand name Trintellix among others, is an antidepressant of the serotonin modulator and stimulator (SMS) class. Its effectiveness is viewed as similar to that of other antidepressants. It is taken orally.
PF-00446687 is a drug developed by Pfizer for the treatment of erectile dysfunction, which is a non-peptide agonist selective for the melanocortin receptor subtype MC4. It was found to be active in preliminary human trials, with the 200mg dose being of similar effectiveness to 100mg sildenafil, though lower doses were ineffective.
PF-592,379 is a drug developed by Pfizer which acts as a potent, selective and orally active agonist for the dopamine D3 receptor, which was under development as a potential medication for the treatment of female sexual dysfunction and male erectile dysfunction. Unlike some other less selective D3 agonists, a research study showed that PF-592,379 has little abuse potential in animal studies, and so was selected for further development and potentially human clinical trials. Development has since been discontinued.
Blarcamesine is an experimental drug which is under development for the treatment of Alzheimer's disease and a variety of other indications.
Buspirone/testosterone (tentative brand name Lybridos) is a combination of buspirone, a 5-HT1A receptor partial agonist, α2-adrenergic receptor antagonist, and D2 autoreceptor antagonist, and testosterone, an androgen or androgen receptor agonist, which is under development by the pharmaceutical company Emotional Brain for the treatment of female sexual dysfunction. Both buspirone and testosterone have individually been found to be effective in the treatment of female sexual dysfunction in clinical studies, and so their combination could be anticipated to be even more effective. As of January 2016, the combination is in phase II clinical trials, with a phase III trial being planned in the United States and Europe.
Drugs and sexual desire is about sexual desire being manipulated through drugs from various approaches. Sexual desire is generated under the effects from sex hormones and microcircuits from brain regions. Neurotransmitters play essential roles in stimulating and inhibiting the processes that lead to libido production in both men and women. For instance, a positive stimulation is modulated by dopamine from the medial preoptic area in the hypothalamus and norepinephrine. At the same time, inhibition occurs when prolactin and serotonin are released for action.