Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malignant syndrome, and, as an adjunct, type 2 diabetes.
Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through different protein interactions. The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors.
The dopamine receptor D4 is a dopamine D2-like G protein-coupled receptor encoded by the DRD4 gene on chromosome 11 at 11p15.5.
Lisuride, sold under the brand name Dopergin among others, is a monoaminergic medication of the ergoline class which is used in the treatment of Parkinson's disease, migraine, and high prolactin levels. It is taken by mouth.
Rotigotine, sold under the brand name Neupro among others, is a dopamine agonist of the non-ergoline class of medications indicated for the treatment of Parkinson's disease and restless legs syndrome. It is formulated as a once-daily transdermal patch which provides a slow and constant supply of the drug over the course of 24 hours.
Etoperidone, associated with several brand names, is an atypical antidepressant which was developed in the 1970s and either is no longer marketed or was never marketed. It is a phenylpiperazine related to trazodone and nefazodone in chemical structure and is a serotonin antagonist and reuptake inhibitor (SARI) similarly to them.
Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups, including those of Solomon H. Snyder and Philip Seeman used a radiolabeled antipsychotic drug to identify what is now known as the dopamine D2 receptor. The dopamine D2 receptor is the main receptor for most antipsychotic drugs. The structure of DRD2 in complex with the atypical antipsychotic risperidone has been determined.
Dopamine receptor D3 is a protein that in humans is encoded by the DRD3 gene.
Amperozide is an atypical antipsychotic of the diphenylbutylpiperazine class which acts as an antagonist at the 5-HT2A receptor. It does not block dopamine receptors as with most antipsychotic drugs, but does inhibit dopamine release, and alters the firing pattern of dopaminergic neurons. It was investigated for the treatment of schizophrenia in humans, but never adopted clinically. Its main use is instead in veterinary medicine, primarily in intensively farmed pigs, for decreasing aggression and stress and thereby increasing feeding and productivity.
Blonanserin, sold under the brand name Lonasen, is a relatively new atypical antipsychotic commercialized by Dainippon Sumitomo Pharma in Japan and Korea for the treatment of schizophrenia. Relative to many other antipsychotics, blonanserin has an improved tolerability profile, lacking side effects such as extrapyramidal symptoms, excessive sedation, or hypotension. As with many second-generation (atypical) antipsychotics it is significantly more efficacious in the treatment of the negative symptoms of schizophrenia compared to first-generation (typical) antipsychotics such as haloperidol.
SB-269970 is a drug and research chemical developed by GlaxoSmithKline used in scientific studies. It is believed to act as a selective 5-HT7 receptor antagonist (EC50 = 1.25 nM) (or possibly inverse agonist). A subsequent study in guinea pig at a concentration of 10 μM showed that it also blocks the α2-adrenergic receptor. The large difference in test concentrations however confirms the selectivity of SB-269970 for the 5-HT7 receptor.
S-15535 is a phenylpiperazine drug which is a potent and highly selective 5-HT1A receptor ligand that acts as an agonist and antagonist at the presynaptic and postsynaptic 5-HT1A receptors, respectively. It has anxiolytic properties.
RDS-127 is a drug which is used in scientific research. It acts as a D2-like receptor agonist and also has some serotonin and adrenergic agonist effects, as well as some anticholinergic action, and produces both anorectic and pro-sexual effects in animal studies.
1-(2-Pyrimidinyl)piperazine (1-PP, 1-PmP) is a chemical compound and piperazine derivative. It is known to act as an antagonist of the α2-adrenergic receptor (Ki = 7.3–40 nM) and, to a much lesser extent, as a partial agonist of the 5-HT1A receptor (Ki = 414 nM; Emax = 54%). It has negligible affinity for the dopamine D2, D3, and D4 receptors (Ki > 10,000 nM) and does not appear to have significant affinity for the α1-adrenergic receptors. Its crystal structure has been determined.
Serotonin antagonist and reuptake inhibitors (SARIs) are a class of drugs used mainly as antidepressants, but also as anxiolytics and hypnotics. They act by antagonizing serotonin receptors such as 5-HT2A and inhibiting the reuptake of serotonin, norepinephrine, and/or dopamine. Additionally, most also antagonize α1-adrenergic receptors. The majority of the currently marketed SARIs belong to the phenylpiperazine class of compounds.
Mepiprazole is an anxiolytic drug of the phenylpiperazine group with additional antidepressant properties that is marketed in Spain. It acts as a 5-HT2A and α1-adrenergic receptor antagonist and inhibits the reuptake and induces the release of serotonin, dopamine, and norepinephrine to varying extents, and has been described as a serotonin antagonist and reuptake inhibitor (SARI). Controlled clinical trials of mepiprazole in patients with irritable bowel syndrome (IBS) were also carried out and suggested some benefits of the drug in relieving symptoms of IBS in some patients. Similarly to other phenylpiperazines like trazodone, nefazodone, and etoperidone, mepiprazole produces mCPP as an active metabolite.
2,3-Dichlorophenylpiperazine (2,3-DCPP or DCPP) is a chemical compound from the phenylpiperazine family. It is both a precursor in the synthesis of aripiprazole and one of its metabolites. It is unclear whether 2,3-DCPP is pharmacologically active as a serotonin receptor agonist similar to its close analogue 3-chlorophenylpiperazine (mCPP), though it has been shown to act as a partial agonist of the dopamine D2 and D3 receptors.
Sonepiprazole (U-101,387, PNU-101,387-G) is a drug of the phenylpiperazine class which acts as a highly selective D4 receptor antagonist. In animals, unlike D2 receptor antagonists like haloperidol, sonepiprazole does not block the behavioral effects of amphetamine or apomorphine, does not alter spontaneous locomotor activity on its own, and lacks extrapyramidal and neuroendocrine effects. However, it does reverse the prepulse inhibition deficits induced by apomorphine, and has also been shown to enhance cortical activity and inhibit stress-induced cognitive impairment. As a result, it 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.
Clocapramine, also known as 3-chlorocarpipramine, is an atypical antipsychotic of the iminostilbene class which was introduced in Japan in 1974 by Yoshitomi for the treatment of schizophrenia. In addition to psychosis, clocapramine has also been used to augment antidepressants in the treatment of anxiety and panic.
Peripherally selective drugs have their primary mechanism of action outside of the central nervous system (CNS), usually because they are excluded from the CNS by the blood–brain barrier. By being excluded from the CNS, drugs may act on the rest of the body without producing side-effects related to their effects on the brain or spinal cord. For example, most opioids cause sedation when given at a sufficiently high dose, but peripherally selective opioids can act on the rest of the body without entering the brain and are less likely to cause sedation. These peripherally selective opioids can be used as antidiarrheals, for instance loperamide (Imodium).
