Burapitant (SSR-240,600) is a drug developed by Sanofi-Aventis which was one of the first compounds developed that acts as a potent and selective antagonist for the NK1 receptor. Burapitant inhibited the binding of radioactive substance P to tachykinin NK1 receptors in human lymphoblastic IM9 cells, human astrocytoma U373MG cells, and human brain cortex. It also showed a subnanomolar affinity for guinea pig NK1 receptors but was less potent on rat and gerbil NK1 receptors. Burapitant inhibited [Sar(9),Met(O2)(11)]substance P-induced inositol monophosphate formation in human astrocytoma U373MG cells. Burapitant (0.1-10 mg/kg i.p. or p.o.) antagonized the excitatory effect of i.c.v. infusion of [Sar(9),Met(O2)(11)]substance P (SP) on the release of acetylcholine in the striatum of anesthetized and awake guinea pigs. This antagonistic action was still observed after repeated administration of Burapitant (5 days, 10 mg/kg p.o., once a day). Burapitant (10 mg/kg i.p.) inhibited the phosphorylation of the cAMP response element-binding protein in various brain regions induced by i.c.v. administration of [Sar9,Met(O2)(11)]SP. While burapitant itself did not proceed beyond early clinical trials and was never developed for clinical use in humans, promising animal results from this and related compounds have led to a number of novel drugs from this class that has now been introduced into medical use.

Paliroden is an orally active drug that activates the synthesis of endogenous neurotrophins or nerve growth factors. Paliroden was investigated in phase II clinical trial in patients with Alzheimer's disease and to evaluate its effect on 18F-Dopa PET imaging in patients with Parkinson's disease. The further development of paliroden was discontinued due to its insufficient efficacy.

Befiradol (also known as NLX-112) was initially developed by Pierre Fabre as a selective serotonin-1A receptor agonist for the treatment of cancer pain and neuropathic pain. However, these trials were discontinued. In 2013, the development and commercialization rights were licensed to Neurolixis. Neurolixis studied befiradol in Parkinson’s disease (PD) patients that exhibit dyskinesia. Dyskinesia is a side effect that appears after several years of action Levodopa, a drug that remains the gold standard treatment for PD. In 2019, FDA gave a positive response to Neurolixis’s befiradol to be tested in Phase 2 clinical in Parkinson's disease patients suffering from debilitating levodopa-induced dyskinesia.