4-Androstadienol

4-Androstadienol (developmental code name PH94B; tentative commercial name Aloradine or Aloradine IN), also known as 4,16-androstadien-3β-ol, is a pherine which is under development by VistaGen Therapeutics, Inc. in a nasal spray formulation ("PRN") for the acute treatment of social anxiety disorder. It is also being investigated by VistaGen Therapeutics for the treatment of generalized anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). The pherine is a positional isomer of the endogenous pheromone androstadienol (5-androstadienol or 5,16-androstadien-3β-ol). As of 2020, it is in phase III clinical trials for social anxiety disorder.
4-Androstadienol lacks affinity for steroid hormone receptors and has instead been found to directly activate isolated human vomeronasal receptor cells at nanomolar concentrations (EC50 = 200 nM).
The pheromone androstenol has been found to act as a potent positive allosteric modulator of the GABAA receptor, and it has been proposed that this action may mediate its pheromone effects. It produces anxiolytic-like effects in animals. Androstadienol, androstadienone, and androstenone, all of which are also pheromones, have been found to be converted into androstenol, and as such, it may be responsible for their pheromone effects. As 4-androstadienol is very closely related structurally to androstadienol, 4-androstadienol might be converted into androstenol similarly and hence potentiation of the GABAA receptor could contribute to its mechanism of action.