Proterguride is a highly potent dopamine receptor agonist with a long duration of action patented by Schering A.-G. for the treatment of Parkinsonism, restless leg syndrome, or the prophylaxis of migraine. According to preclinical studies, Proterguride, unlike most dopamine receptor agonist, is suitable for transdermal administration. Especially in the case of dopamine agonists, the transdermal route of administration might become of great clinical importance due to the ability to achieve constant plasma levels and, thus, to imitate the physiological continuous release profile of dopamine. Pulsatile stimulation of dopaminergic receptors as it occurs with oral administration of dopaminergic drugs is considered the cause of treatment-associated motor complications.

Citatepine is an antagonist of dopamine receptors. It attenuated dopamine-agonist induced behavioral stimulation (stereotypies in rats or climbing in mice). The compound displayed preferential action on hippocampal DA receptors as compared to the striatum. In addition, it shows antihistaminergic, antiserotonergic, anticholinergic and adrenolytic effects. The drug was investigated in the clinic for the treatment of schizophrenia. It was expected that this drug would show an antipsychotic efficacy in doses not causing extrapyramidal side-effects. This expectation has not been fulfilled.

Radafaxine (GW353162, ( )-(2S,3S)-2-(3-chlorophenyl-3,5,5-trimethyl-2-morphinol) or S,S-hydroxybupropion) is an active metabolite of bupropion. It acts as an inhibitor of the dopamine transporter. Radafaxine was investigated for the treatment of depression however, development was discontinued.

Aplindore (DAB-452) is a small molecule that displays potent dopamine D2 receptor partial agonist activity in in vitro and in vivo assays and is predicted to have antipsychotic efficacy without motor side effects. Aplindore had been in phase II clinical trials for the treatment of Parkinson's disease and restless legs syndrome. Aplindore was generally well tolerated and there were no withdrawals due to adverse events and no serious adverse events.

Cliropamine (D 16427) is a positive inotropic compound.

Sonepiprazole exhibits highly specific binding to the D4 dopamine receptor with more than 100-fold selectivity for the D4 receptor over other receptors, including dopamine, serotonin, and adrenergic receptors. It is a neutral antagonist at the D4 dopamine receptor and is devoid of dopamine agonist activity. Sonepiprazole selectively induces c-fos expression in the prefrontal cortex and blocks behavioral, biochemical, and genomic effects of repeated amphetamine administration in rats. Sonepiprazole was investigated as an antipsychotic for the treatment of schizophrenia in a placebo-controlled clinical trial, but in contrast to its comparator olanzapine no benefits were found and it was not researched further for this indication.

Spirilene is an antipsychotic agent. In rabbit caudate nucleus (CN) spirilene exhibited Ki value of 3.5 uM at the 5-HT1R site, but produced less than 50% inhibition of [3H]5-HT binding to the 5-HT1D site even at concentrations as high as 100 uM.

Fosopamine (also known as Sim 2055), is a prodrug of epinine was studied for the treatment of renal failure and of essential hypertension. However, phase II of clinical trials in Italy was discontinued in 1995. Information about the current development of this drug is not available.

Vanoxerine, also known as GBR-12909, is a piperazine derivative exhibiting potent selective inhibition of sodium-dependent dopamine reuptake transporters. Vanoxerine has been in clinical trials for Parkinsonism, depression and cocaine addiction but lacked efficacy. Vanoxerine has also been observed as a potent blocker of the following channels: cardiac hERG/IKr potassium channel, Calcium channel, voltage-dependent, L type, alpha 1C subunit (also known as Cav1.2) and voltage-gated sodium channel Nav 1.5. Vanoxerine was studied as a potential treatment for atrial fibrillation. However, phase III clinical trials for this condition were terminated because of cardiac safety concerns. Research also indicates that vanoxerine may have additional mechanisms of action including antagonist action at nicotinic acetylcholine receptors (nAChRs).

Tiomergine is an ergot alkaloid derivative. It is the agonist of the postulated presynaptic dopamine receptor. Tiomergine is the antiparkinsonian agent. Tiomergine modified brain glucose metabolism in a way similar to the neuroleptics but different from postsynaptic agonists. It was ineffective in the treatment of tardive dyskinesia.