Propylnorapomorphine is a potent and selective D2 receptor agonist. Propylnorapomorphine is used as a tool compound to label dopamine receptors in rodent brain, and elicits dopaminergic behavioural effects. It stimulates motor activity, induces stereotypic behaviour and sexual stimulation. Propylnorapomorphine was investigated in clinical trial against Parkinson's disease and schizophrenia

Pergolide is a long-acting dopamine agonist approved in 1982 for the treatment of Parkinson’s Disease. It is an ergot derivative that acts on the dopamine D2 and D3, alpha2- and alpha1-adrenergic, and 5-hydroxytryptamine (5-HT) receptors. It was indicated as adjunct therapy with levodopa/carbidopa in the symptomatic treatment of parkinsonian syndrome. It was later found that pergolide increased the risk of cardiac valvulopathy. The drug was withdrawn from the US market in March 2007 and from the Canadian market in August 2007. Pergolide stimulates centrally-located dopaminergic receptors resulting in a number of pharmacologic effects. Five dopamine receptor types from two dopaminergic subfamilies have been identified. The dopaminergic D1 receptor subfamily consists of D1 and D5 subreceptors and are associated with dyskinesias. The dopaminergic D2 receptor subfamily consists of D2, D3 and D4 subreceptors and has been associated with improvement of symptoms of movement disorders. Thus, agonist activity specific for D2 subfamily receptors, primarily D2 and D3 receptor subtypes, are the primary targets of dopaminergic antiparkinsonian agents. It is thought that postsynaptic D2 stimulation is primarily responsible for the antiparkinsonian effect of dopamine agonists, while presynaptic D2 stimulation confers neuroprotective effects. This semisynthetic ergot derivative exhibits potent agonist activity on dopamine D2- and D3-receptors. It also exhibits agonist activity on dopamine D4, D1, and D5, 5-hydroxytryptamine (5-HT)1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, α2A-, α2B-, α2C-, α1A-, α1B-, and α1D-adrenergic receptors. Parkinsonian Syndrome manifests when approximately 80% of dopaminergic activity in the nigrostriatal pathway of the brain is lost. As this striatum is involved in modulating the intensity of coordinated muscle activity (e.g. movement, balance, walking), loss of activity may result in dystonia (acute muscle contraction), Parkinsonism (including symptoms of bradykinesia, tremor, rigidity, and flattened affect), akathesia (inner restlessness), tardive dyskinesia (involuntary muscle movements usually associated with long-term loss of dopaminergic activity), and neuroleptic malignant syndrome, which manifests when complete blockage of nigrostriatal dopamine occurs. High dopaminergic activity in the mesolimbic pathway of the brain causes hallucinations and delusions; these side effects of dopamine agonists are manifestations seen in patients with schizophrenia who have overractivity in this area of the brain. The hallucinogenic side effects of dopamine agonists may also be due to 5-HT2A agonism. The tuberoinfundibular pathway of the brain originates in the hypothalamus and terminates in the pituitary gland. In this pathway, dopamine inhibits lactotrophs in anterior pituitary from secreting prolactin. Increased dopaminergic activity in the tuberoinfundibular pathway inhibits prolactin secretion. Pergolide also causes transient increases in somatotropin (growth hormone) secretion and decreases in luteinizing hormone (LH) concentrations. Pergolide is not available for use by humans in the United States, but approved for veterinary use; it was used in various other countries for the treatment of various conditions including Parkinson's disease, hyperprolactinemia, and restless leg syndrome. Pergolide in Europe was indicated for Parkinson's disease only when other dopaminergic agonist treatments had failed, and treatment had to be initiated by a neurologist. The label warned against using doses of more than 5mg a day, whether alone or in combination with levodopa. However the marketing of this drug finally stopped in France in May 2011 and sales elsewhere in Europe ceased eventually.

Domperidone is a peripherally selective D2 receptor antagonist. It acts as an antiemetic and a prokinetic agent through its effects on the chemoreceptor trigger zone and motor function of the stomach and small intestine. Domperidone was not approved in USA due to risks of cardiac arrhythmias, cardiac arrest, and sudden death, but is available in other countries. However, FDA allows access to Domperidone through an expanded access investigational new drug application (IND) to patients with gastroesophageal reflux disease with upper GI symptoms, gastroparesis, and chronic constipation. As an “off-label” use, domperidone is prescribed to breastfeeding women to enhance their milk production.

Domperidone is a peripherally selective D2 receptor antagonist. It acts as an antiemetic and a prokinetic agent through its effects on the chemoreceptor trigger zone and motor function of the stomach and small intestine. Domperidone was not approved in USA due to risks of cardiac arrhythmias, cardiac arrest, and sudden death, but is available in other countries. However, FDA allows access to Domperidone through an expanded access investigational new drug application (IND) to patients with gastroesophageal reflux disease with upper GI symptoms, gastroparesis, and chronic constipation. As an “off-label” use, domperidone is prescribed to breastfeeding women to enhance their milk production.

Sulpiride is an atypical antipsychotic drug (although some texts have referred to it as a typical antipsychotic) of the benzamide class used mainly in the treatment of psychosis associated with schizophrenia and major depressive disorder, and sometimes used in low dosage to treat anxiety and mild depression. Sulpiride is commonly used in Europe, Russia and Japan. Sulpiride is a selective antagonist at dopamine D2 and D3 receptors. This action dominates in doses exceeding 600 mg daily. In doses of 600 to 1,600 mg sulpiride shows mild sedating and antipsychotic activity. Its antipsychotic potency compared to chlorpromazine is only 0.2 (1/5). In low doses (in particular 50 to 200 mg daily) its prominent feature is antagonism of presynaptic inhibitory dopamine receptors accounting for some antidepressant activity and a stimulating effect. Therefore, it is in these doses used as a second line antidepressant. Racemic and L-sulpiride significantly decreased stimulated serum gastrin concentration, but they did not affect fasting serum gastrin or basal and stimulated gastric acidity. D-sulpiride significantly decreased gastric acid secretion, without affecting serum gastrin levels.

Clocapramine is a chlorinated derivative of carpipramine. The hydrochloride has been given orally in the treatment of schizophrenia. Clocapramine is an antagonist of the Dopamine D2 and Serotonine (5-HT2) receptors. It has been implicated in at least one strange death, including a suicide. It augments the paroxetine in the panic disorder treatment.

Cyamemazine (Tercian), also known as cyamepromazine, is a typical antipsychotic drug of the phenothiazine class used primarily in the treatment of schizophrenia and psychosis-associated anxiety. Cyamemazine actually behaves like an atypical antipsychotic, due to its potent anxiolytic effects and lack of extrapyramidal side effects. Cyamemazine is used for the treatment of chronic psychotic states, anxiety, major depression.

Mosapramine (Cremin) is used to treat chronic schizophrenia in Japan. It is a potent dopamine antagonist with high affinity to the dopamine receptor subtypes 2, 3 and 4, and with moderate affinity for the 5-HT2 receptors

Roxindole (EMD-49,980) is a dopaminergic and serotonergic drug which was originally developed for the treatment of schizophrenia. Roxindole has also been investigated as a therapy for the major depressive disorder, Parkinson's disease, and prolactinoma. Roxindole is dopamine autoreceptor-selective agonistic drug with high affinity to D2-like receptors and with much lower affinities to D1-like, % and ol2, muscarinic and 5HT 2 receptors. Additionally, Roxindole exerts 5HT uptake inhibition and 5HT1A agonistic effects. The bioavailability of Roxindole has been estimated at 5% due to a high first-pass metabolization. On the other hand, in 14C distribution studies, Roxindole has crossed the blood-brain barrier readily and the brain concentrations at all intervals have been much higher than corresponding plasma levels. In clinical trials, Roxindole ‘s antipsychotic efficacy was only modest but it was unexpectedly found to produce potent and rapid antidepressant and anxiolytic effects. However, the clinical development of Roxindole was discontinued.

Sultopride (trade names Barnetil, Barnotil, Topral) is an atypical antipsychotic of the benzamide chemical class used in Europe, Japan, and Hong Kong for the treatment of schizophrenia. It was launched by Sanofi-Aventis in 1976. Sultopride acts as a selective D2 and D3 receptor antagonist. It has also been shown to have clinically relevant affinity for the GHB receptor as well, a property it shares in common with amisulpride and sulpiride.