Neuropeptide

Kisspeptin-10 is the shortest natural form of kisspeptin, the hypothalamic hormone that switches on the reproductive axis. It is the ten amino acids at the end of the longer kisspeptins and keeps their full activity at the kisspeptin receptor. A single injection releases GnRH and so LH within minutes, and infusions raise testosterone in healthy men and in men with type 2 diabetes and low testosterone. It clears from the blood in about 4 minutes, so studies have used infusions, and its effects in women depend on the phase of the menstrual cycle. It is not approved for any use.

Oxytocin is a nine-amino-acid hormone made in the hypothalamus. It contracts the uterus in labor and releases milk, and in the brain it acts on social, sexual and stress behavior through a single receptor. Injected oxytocin is a standard drug for preventing bleeding after birth. As a nasal spray it raised oxytocin in the cerebrospinal fluid, but the large trials of intranasal oxytocin in autism and obesity were negative, a famous finding that it increases trust failed to replicate, and it did no better than placebo for women's sexual function.

VIP - vasoactive intestinal peptide - is a 28-amino-acid neuropeptide the body makes, densely present in the lung, where it relaxes smooth muscle, dilates pulmonary vessels and restrains inflammation. As a drug it is called aviptadil, and it has been tried in three quite different settings with three different outcomes. Inhaled VIP in sarcoidosis was safe and produced measurable immunoregulatory effects in an open phase 2 study. Inhaled aviptadil in pulmonary hypertension gave modest hemodynamic changes in a 20-patient study. And in COVID-19 respiratory failure, one 196-patient randomized trial reported a survival benefit at 60 days while the larger, better-powered TESICO trial found nothing. That sequence - promising small trial, null large trial - is the most informative thing about it.