Diethylthiambutene is an analgesic agent with an effect like that of morphine. Diethylthiambutene mainly used in veterinary. It is highly toxic to cats. Can cause convulsions if injected intravenously. Diethylthiambutene is a synthetic opioid drug. It is under international control according to the UN Single Convention 1961 and its amendments, schedule I.

Ruzadolane (previously known as UP 26-91) is a serotonin receptor antagonist that was developed as a non-narcotic, centrally acting analgesic agent for the treatment of anxiety disorder and pain. However, these studies were discontinued.

Indantadol (previously known as CHF-3381) is an oral and noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist and reversible monoamine oxidase-A (MAO-A) inhibitor that is being developed by Vernalis plc, under license from Chiesi Farmaceutici SpA, for the potential treatment of neuropathic pain. In preclinical studies, indantadol exhibited neuroprotective effects after kainate-induced seizures and displayed anticonvulsant and antihyperalgesic activity. Indantadol also caused a dose-dependent decrease in exploratory motility. In a human heat-capsaicin-induced pain model, indantadol at a dose of 500 mg effectively reduced the area of secondary hyperalgesia. The tolerability profile of the drug at single doses up to 600 mg and twice-daily doses up to 400 mg in clinical trials was significantly more favorable than for other NMDA antagonists. Most side effects have been observed to be mild, and include dizziness and asthenia. Indantadol was in phase II clinical trials for the treatment of chronic cough and neuropathic pain. However, these studies had been discontinued.

Pexacerfont is a highly potent and selective CRF1 receptor antagonist that displays no agonist properties. It is specific for CRF1 receptors and has more than 1,000- fold less affinity for CRF2 receptors, and more than 100- fold less affinity for the CRF-binding protein. In extensive preclinical studies, pexacerfont has been shown to inhibit specific binding of CRF to rat, dog, monkey, and human CRF1 receptors. The functional anxiolytic effects of CRF1 receptor occupancy were demonstrated in two rodent models of anxiety, situational anxiety and elevated plus maze paradigms. Pexacerfont did not demonstrate efficacy compared to placebo for the treatment of generalized anxiety disorder in human. The bogus taste tests suggested some protective effect of pexacerfont against eating after a laboratory stressor. Pexacerfont had been in phase II clinical trials for the treatment of irritable bowel syndrome and depression depression.

Ethylmethylthiambutene is a potent analgesic compatible with morphine. It possesses addiction liability similar to that of morphine.

Brequinar is a synthetic quinolinecarboxylic acid analogue with antineoplastic properties. Brequinar inhibits the enzyme dihydroorotate dehydrogenase, thereby blocking de novo pyrimidine biosynthesis. This agent may also enhance the in vivo antitumor effect of antineoplastic agents such as 5-FU. Brequinar had been in phase II clinical trials by Bristol-Myers Squibb for the treatment of cancer and transplant rejection. However, this research has been discontinued. Brequinar had been also in preclinical studys for the treatment of cytomegalovirus infections. However, this research has been discontinued.

Bicifadine (DOV-220075) is not a narcotic and is well-tolerated and, in preclinical studies, has been shown not to act at any opiate receptor, but inhibits monoamine neurotransmitter uptake by recombinant human transporters in vitro with a relative potency of norepinephrine:serotonin:dopamine of 1:2:17. Bicifadine was in Phase II clinical trial for pain caused by diabetic neuropathy, in addition, was in phase III clinical trial to treat Chronic Low Back Pain, but that studies were discontinued

Relcovaptan is a potent, orally active nonpeptide vasopressin V1a antagonist that was undergoing clinical development with Sanofi-Synthélabo (formerly Sanofi) in France. SR49059 is specifically and selectively antagonizes the effect of vasopressin on the V1a receptor in animals’ and in humans. The drug has been shown to have an excellent safety profile in single and repeated dose toxicological studies in animals. In the human uterus in vitro, SR49059 caused a dose-dependent inhibition of vasopressin V1a receptor-mediated activity of myometrial strips and isolated uterine arteries. In vivo in nonpregnant women, an inhibition of vasopressin-induced uterine activity has been observed.

Cutamesine, an agonsit of brain sigma 1 receptors, was developed by Santen Pharmaceutical for the treatment of cognitive diseases. The drug was tested in phase II in patients with major depressive disorders and for recovery of patients with stroke, however its development was terminated for the given conditions. Currently M's science corporation is developing cutamesine for Amyotrophic lateral sclerosis and Retinitis pigmentosa as more suitable target diseases.