4-{2-[5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine (S1RA, E-52862) is an 1-arylpyrazole class of sigma-1 receptor antagonist. Formalin-induced nociception (both phases), capsaicin-induced mechanical hypersensitivity and sciatic nerve injury-induced mechanical and thermal hypersensitivity were dose-dependently inhibited by systemic administration of S1RA. Occupancy of sigma-1 receptors in the CNS was significantly correlated with the antinociceptive effects. As a mechanistic correlate, electrophysiological recordings demonstrated that pharmacological antagonism of sigma-1 receptors attenuated the wind-up responses in spinal cords sensitized by repetitive nociceptive stimulation. Esteve is developing E 52862 for the treatment of several pain indications, including diabetic neuropathies, chemotherapy-induced neuropathic pain, postherpetic neuralgia, postoperative pain. Phase II development of this first-in-class agent is underway in Romania, Spain and Greece.

Acetophenazine (Tindal) is an antipsychotic drug of moderate-potency. Used in the treatment of disorganized and psychotic thinking. Acetophenazine (Tindal) is also used to help treat false perceptions (e.g. hallucinations or delusions). Acetophenazine acts as an antagonist of dopaminergic D2 receptors in the brain. Acetophenazine exhibited modest androgen receptor binding and antiandrogen activity.

Nalorphine has a mixed opioid agonist-antagonist properties. Nalorphine inhibits the cholinesterases of mouse brain, bovine erythrocytes and horse serum. It acts on mu-, k- and sigma-opioid receptors. Nalorfin by virtue of the agonistic effect has an analgesic effect but to a much lesser extent than morphine. Initially, before the appearance of a "pure" morphine-naloxone antagonist, nalorphine was used as an antidote for severe respiratory depression and other body function disorders caused by acute poisoning in case of an overdose of morphine, promedol, fentanyl or other narcotic analgesics, or with increased sensitivity to them. At present, nalorphine is practically not used for this purpose. It was replaced by naloxone. Large doses of nalorphine can cause nausea, cramps, drowsiness, headache, mental stimulation.

Xylazine was developed as an antihypertensive agent. During clinical studies in people xylazine was found to have excessive central nervous system depressant effects and it was subsequently introduced for veterinary use as a sedative, analgesic and relaxant. Xylazine is a potent alpha-2 adrenergic agonist. Xylazine in horses and Cervidae may occasionally cause slight muscle tremors, bradycardia with partial A-V heart block and a reduced respiratory rate. Movement in response to sharp auditory stimuli may be observed.

Fabomotizole (also known as Afobazole) is a selective non-benzodiazepine anxiolytic which was developed in Russia and launched in 2006. The drug is used for the treatment of wide range of diseases: generalized anxious disorders, neurasthenia, adaptation disorders, sleep disorders, for alleviation of withdrawal syndrome. According to the drug label (in Russian), its action is related to the interaction with sigma-1 receptors.

Remoxipride is a substituted benzamide. It is a weak, but relatively selective, central dopamine D2-receptor antagonist and appears to have preferential affinity for extrastriatal dopamine D2-receptors. It also has marked affinity for central sigma receptors. It was introduced by Astra (Roxiam) at the end of the eighties and was prescribed as an atypical antipsychotic. Remoxipride was withdrawn from the market worldwide by Astra because of several cases of aplastic anaemia associated with the drug.

Ifenprodil (marketed under the brands Vadilex; Dilvax; Creocral; Cerocral) is a selective NMDA receptor (glutamate) antagonist. Additionally, ifenprodil inhibits GIRK channels, and interacts with alpha1 adrenergic, serotonin, and sigma receptors. Ifenprodil acts as a vasodilator. Ifenprodil is a medicine available in a number of countries worldwide, but not in US.