Tiprenolol (DU21445) has been shown by both in vitro and in vivo animal experiments, to possess strong beta-adrenergic blocking but a relatively less strong negative inotropic activity. The same report also demonstrated by its inhibiting influence on spontaneous mobility of rat uterus, an intrinsic beta-sympathomimetic activity. Tiprenolol reveals effects similar to propranolol. Tiprenolol was shown to have significantly less heart rate slowing effect at rest than propranolol. However, all other measurements failed to show any difference of statistical significance between the two drugs with respect to any negative inotropic or beta‐blocking activity. The administration of tiprenolol or propranolol depressed the arterial pressure and caused the deaths of some dogs in which a coronary artery had been ligated.

Trefentanil is a short-acting synthetic opioid of the piperidine class. The drug caused potent analgesia with the peak effect occurring 3 min after injection. There was no significant difference in analgesic potency of trefentanil and alfentanil as measured by tolerance to tibial pressure at 3 min. Trefentanil had a pharmacokinetic and pharmacodynamic profile similar to alfentanil, with a small extent of tissue distribution and a rapid blood/brain equilibration. Trefentanil caused significant respiratory depression at doses of 32 ug/kg and 64 ug/kg. It is a mu-opioid receptor agonist. Trefentanil produced naloxone reversible anti-nociception equi-efficacious to that of fentanyl.

Talsaclidine (WAL-2014) is a selective full agonist of M1 muscarinic receptor, having partial agonist activity on the M2 and M3 subtypes (with no in vivo consequences). The general receptor profile of talsaclidine demonstrates a nearly specific interaction with muscarinic receptors, having only weak binding affinity for alpha1- and nicotinic receptors. The drug is being tested in phase III of clinical trials for the treatment of Alzheimer's disease.

Carbazocine is an opioid analgesic of the benzomorphan family which was never marketed

The selective kappa-opioid receptor agonist spiradoline (U62,066E), an arylacetamide, was synthesized with the intention of creating an analgesic that, while still retaining its analgesic properties, would be devoid of the, mainly mu receptor mediated, side effects such as physical dependence and respiratory depression associated with morphine. The racemate spiradoline was found to be highly selective for the kappa receptor, with a Ki of 8.6 nM in the guinea pig. Examination of the enantiomers of spiradoline, showed the (-)enantiomer to be responsible for the kappa agonist properties. Spiradoline easily penetrates the blood brain barrier, and does not seem to have any significant active metabolites. In preclinical studies, spiradoline has a short duration of action with a peak at around 30 min after administration. The analgesic properties of spiradoline are well documented in mice and rats. Antitussive properties have also been reported in rats. Spiradoline was reported to display effects suggestive of neuroprotective properties in animal models of ischemia. In humans, spiradoline is a potent diuretic. It also produces significant sedation presumably due to its antihistamine properties. Preclinical studies have shown that spiradoline reduces blood pressure and heart rate, and has possible antiarrhythmic properties. Clinical studies did not confirm these findings. Although spiradoline had promising effects in animal tests of analgesia, and a reasonably good safety profile in preliminary studies, it did not replace morphine as an analgesic. The available clinical data suggest that spiradoline produces disturbing adverse effects such as diuresis, sedation, and dysphoria at doses lower than those needed for analgesic effects. Spiradoline was in phase II clinical trials with Pharmacia & Upjohn in Japan and the USA, principally for the treatment of pain. However, the commercial development of spiradoline has been discontinued.

Roflurane (DA-893) is a fluorinated ether and general inhalation anesthetic. In humans, this compound shows less hypotensive effects than methoxyflurane. Roflurane was never marketed.

Quinelorane is an octahydropyrimido[4,5-g]quinolone derivative patented by American pharmaceutical company Eli Lilly and Co. as for the treatment anxiety, Parkinson's syndrome, depression, and hypertension. Quinelorane acts as an agonist of dopamine agonist for the D2 and D3 receptors. In preclinical studies Quinelorane (IM) treatment produced dose-dependent effects on male sexual responding. Penile erections and masturbation were markedly facilitated following treatment with either 2.5 or 5 micrograms/kg quinelorane. Higher doses of quinelorane (10 and 25 micrograms/kg) generally did not further augment sexual responding but rather resulted in a return in sexual responding to control vehicle levels. Quinelorane had a biphasic effect on yawning behavior of the monkeys with low doses (2.5 and 5 micrograms/kg) facilitating yawning and high doses (25 micrograms/kg) inhibiting yawning.

Isoindoline pazinaclone (also known as DN-2327), a partial agonist at GABAA benzodiazepine receptors, produced anxiolytic, taming and anti-convulsive effects. This neuropsychiatric drug was involved in phase II clinical trial for patients with generalized anxiety disorder. However, this study was discontinued.

Serazapine (CGS15040) is an anxiolytic agent. It is structurally novel 5-HT2 receptor antagonist. Preliminary preclinical findings indicated an anticonflict effect in a behavioral suppression test, and two preliminary investigations in volunteers also suggested anxiolytic potential. In the first of these studies serazapine resembled diazepam, a reference anxiolytic drug, electroencephalographically. Additionally, in a test of psychogenic stress in volunteers it reduced cardiac output.

Milameline (previously known as RU 35926/CI-979), a partial muscarinic agonist that was developed as a cognition-enhancing agent for the treatment of patients with Alzheimer's disease. In spite of this drug has achieved phase III clinical trials, further studies were apparently discontinued.