AstraZeneca R&D Charnwood (formerly Astra Charnwood, a subsidiary of AstraZeneca) was developing sibenadet (Viozan, AR-C68397AA) for the potential treatment of chronic obstructive pulmonary disease and asthma. Sibenadet is a dual D2 dopamine receptor, beta2-adrenoceptor agonist that combines bronchodilator activity with the sensory afferent modulating effects associated with D2-receptor agonism. Development of sibenadet has been discontinued due to disappointing efficacy findings.

Quinpirole (LY 171,555) is a psychoactive drug and research chemical which acts as a selective D2 and D3 receptor agonist. Quinpirole is the most widely used D2 agonist in in vivo and in vitro studies. Specific quinpirole binding in rat brain was saturable, and dependent on temperature, membrane concentration, sodium concentration and guanine nucleotides. Saturation analysis revealed high affinity binding characteristics (KD = 2.3 nM) which were confirmed by association-dissociation kinetics. The regional distribution of [3H]quinpirole binding sites roughly paralleled the distribution of [3H]spiperone binding sites, with greatest densities present in the striatum, nucleus accumbens and olfactory tubercles. A variety of drugs, most notably monoamine oxidase inhibitors (MAOls), inhibit the binding of [3H]quinpirole, but not [3H]spiperone or [3H](-)N-n-Propylnorapomorphine, in rat striatal membranes by a mechanism that does not appear to involve the enzymatic activity of MAO. Clinically antidepressant MAOIs exhibited selectivity between sites labeled by [3H]quinpirole and [3H]spiperone as did a number of structurally related propargylamines and N-acylethylenediamine derivatives and other drugs such as debrisoquin and phenylbiguanide. Quinpirole has been shown to increase locomotion and sniffing behavior in mice and induces compulsive behavior symptomatic of obsessive compulsive disorder in rats.

Neflumozide is an antipsychotic.

Pinoxepin belongs to the dibenzoxepine series of drugs which are characterized by a 6-7-6 tricyclic nuclear structure. Clinical studies indicated that pinoxepin was a potent antipsychotic-sedative equally effective to chlorpromazine and thioridazine. Pinoxepin in studies with chronic schizophrenic patients displayed useful effects on behavior without unduly prominent side effects. In doses above 300 mg seizures are reported and more frequent changes in liver-function tests were noted than with standard drug, but below 300 mg pinoxepin was found to have side effects similar to chlorpromazine and marked sedative effects.

Trepipam is a benzazepine derivative. It is a D1-dopamine antagonist. Trepipam significantly reduced aggression in behaviorally disturbed adolescents and in acute schizophrenics without producing concomitant sedation. Trepipam specifically reduces aggressive and hyperactive behaviors in a wide range of laboratory tests in various species, without producing signs of overt CNS depression or neurological impairment. The drug is effective in reducing many forms of aggression including brain stimulated emotional behavior. Trepipam actually had little effect on gross behavior in mice or rats and only produced ataxia at lethal doses.

Butaclamol is an antipsychotic drug, which was studied for the treatment of schizophrenia. This drug has never marketed and now is used in research, because of its action as a dopamine receptor-blocking agent. Butaclamol consists of the two forms: (-)-butaclamol, an inactive drug and (+)-butaclamol, a potent neuroleptic drug.

Lergotrile is an ergot alkaloid clinically effective in the treatment of Parkinson’s disease. The in vivo dopaminergic effects of lergotrile are similar to those produced by the direct acting dopaminergic agonists apomorphine or L-DOPA. Like apomorphine or L-DOPA, lergotrile decreases prolactin secretion, produces stereotyped behavior in intact rats, and causes contralateral rotation in rats with uniIateral 6-hydroxydopamine lesions of substantia nigra. However, unlike apomorphine or L-DOPA, lergotrile does not activate dopamine sensitive adenylate cyclase in vitro. Side effects of lergotrile included exacerbation of hallucinations, dyskinesias, hypotension, and alterations in liver function tests. Although lergotrile, when added to levodopa, has a definite antiparkinsonian effect, the incidence of adverse effects, particularly hepatotoxicity, makes it unlikely that this ergot alkaloid will become widely available for the treatment of Parkinson’s disease.

Solypertine (WIN-18413-2) is an antiadrenergic drug. Solypertine selectively blocked the conditioned avoidance response in rats. Solypertine potentiated hexobarbitone sleeping time, caused hypothermia and afforded protection from amphetamine toxicity inaggregated mice.