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.

Trifluperidol is an antipsychotic butyrophenone derivative. It is a high-affinity sigma receptor blocker and it was strongly selective for NR1a/2B receptors. It exhibit pharmacological effects and a mechanism of action very similar to that of phenothiazines and thioxanthenes in that it blocks dopaminergic receptors. It is more selective with respect to D2 receptors. Trifluperidol is indicated for the treatment of acute and chronic schizophrenia, mania and hypomania, organic psychoses, childhood behavioral disorders, agitation in psychotic illness and motor tics. Trifluperidol has been suspected as a cause of cataract in Japan. Patients receiving trifluperidol treatment may develop a parkinsonian-like syndrome which responds to withdrawal of the drug or concurrent administration of an anti-parkinsonian drug. Acute dystonias and akathisia are other acute extrapyramidal effects; tardive dyskinesia may supervene after longer periods of treatment.

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.

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.

Zuclomiphene Citrate is the cis isomer of clomiphene which exhibits weak estrogen agonist activity evaluated for antineoplastic activity against breast cancer. The individual isoforms are not available commercially, but Repros Therapeutics (The Woodlands, TX, USA) has separated them and is using enclomiphene citrate (ENC) in clinical trials in men with secondary hypogonadism who wish to preserve their fertility. Zuclomiphene, possessing no oestrogen antagonism at physiological concentrations, appears to have a longer biological half-life than enclomiphene, and thus may persist for long periods in the body. At high concentrations zuclomiphene can act as an oestrogen agonist. Clomiphene citrate (CC) is often used ‘off-label’ in men who have low testosterone to raise levels, it is also useful for the restoration of sperm counts in men. CC is approved by FDA and widely used in women for induction of ovulation for several conditions. CC is a mixture of two diastereoisomers, a cis isomer, zuclomiphene citrate (ZUC, 38%) and a trans isomer, ENC (62%). The two clomiphene isomers have mixed estrogenic and antiestrogenic effects that vary among species.

Opipramol (Insidon, Pramolan, Ensidon, Oprimol) is an antidepressant and anxiolytic used in Germany and other European countries. Although it is a member of the tricyclic antidepressants, opipramol's primary mechanism of action is much different in comparison, it doesn’t represent a tricyclic antidepressant drug as it does not inhibit the neuronal uptake of norepinephrine and/or serotonin. Opipramol also acts as a low to moderate affinity antagonist for the D2, 5-HT2, H1, H2, and muscarinic acetylcholine receptors. H1 and H2 receptor antagonism account for its antihistamine effects, and muscarinic acetylcholine receptor antagonism is responsible for its anticholinergic properties. Opipramol was developed by Schindler and Blattner in 1961. Opipramol is typically used in the treatment of generalized anxiety disorder (GAD) and somatoform disorders. Its anxiolysis becomes prominent after only one to two weeks of chronic administration. Upon first commencing treatment, opipramol is rather sedating in nature due to its antihistamine properties, but this effect becomes less prominent with time. The therapy with Opipramol indicates an additional therapy with neuroleptics, hypnotics and tranquilizers (e.g. Barbiturates, Benzodiazepines). Therefore, it should be noted that some specific reactions, particularly CNS depressant effects could be intensified and an intensification of common side effects may occur. If necessary the dosage may be reduced. Co-administration with alcohol can cause stupor. MAO Inhibitors should be discontinued at least 14 days before the treatment with Opipramol. Concomitant use of Opipramol with β-blockers, antiarrhythmics (of class 1c), as well as drugs from tricyclic antidepressant group and preparations which influence the microsomal enzyme system, can lead to change in plasma concentration of these drugs. Co-administration of neuroleptics (example- haloperidol, risperidone) can increase the plasma concentration.

Dextromethorphan is a non-narcotic morphine derivative widely used as an antitussive for almost 40 years. It has attracted attention due to its anticonvulsant and neuroprotective properties. It is a cough suppressant in many over-the-counter cold and cough medicines. In 2010, the FDA approved the combination product dextromethorphan/quinidine for the treatment of pseudobulbar affect. Dextromethorphan suppresses the cough reflex by a direct action on the cough center in the medulla of the brain. Dextromethorphan shows high-affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist and acts as a non-competitive channel blocker. It is one of the widely used antitussives and is used to study the involvement of glutamate receptors in neurotoxicity. Dextromethorphan (DM) is a sigma-1 receptor agonist and an uncompetitive NMDA receptor antagonist. The mechanism by which dextromethorphan exerts therapeutic effects in patients with pseudobulbar affect is unknown. Dextromethorphan should not be taken with monoamine oxidase inhibitors due to the potential for serotonin syndrome. Dextromethorphan is extensively metabolized by CYP2D6 to dextrorphan, which is rapidly glucuronidated and unable to cross the blood-brain barrier.