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Trade names | Norprolac |
AHFS/Drugs.com | International Drug Names |
Routes of administration | Oral |
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Chemical and physical data | |
Formula | C20H33N3O3S |
Molar mass | 395.56 g·mol−1 |
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Quinagolide (INN , BAN ), sold under the brand name Norprolac, is a selective dopamine D2 receptor agonist which is used to reduce elevated levels of prolactin (hyperprolactinemia). [1] It has also been found to be effective in the treatment of breast pain. [2] It is used in the UK, but it is not available in US.
Quinagolide is a racemate composed of the following two enantiomers: [3]
Enantiomeres of Quinagolide | |
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(+)-Quinagolid CAS number: 140630-79-1 | (-)-Quinagolid CAS number: 140630-80-4 |
The first synthesis of quinagolide was disclosed in patents filed by Sandoz. [4]
A sequence of nine steps is required to transform the starting material 5-methoxy-2-tetralone (1) into the octahydrobenzo[g]quinoline ring system with the correct stereochemistry required. This intermediate (11) is then converted in another five steps to the drug. Transformation of the ester (13) into the amine (15) is accomplished by a Curtius rearrangement in which an acyl hydrazide is treated with nitrosyl chloride. [4] [5] [6]
The laboratory route was not practical for the synthesis of quinagoline on a large scale. Therefore scientists at Novartis developed an improved process. [7]
The starting material is 1,6-dimethoxynaphthalene (1). This is selectively lithiated at the C-7 position and reacts with (2Z)-ethyl 2-cyano-3-ethoxyacrylate (2), to give the cyanoacrylate (3). Catalytic hydrogenation and hydrolysis produces (5). Birch reduction of (5) leads first to (6) which on acid work-up gives the imine (7), which is reduced with sodium borohydride to yield (8). Fischer esterification with methanol gives an ester that is next alkylated with 1-iodopropane to give (11). The required stereochemistry for quinagoline is set in the final steps. [7] [8] [9]
Salvinorin A is the main active psychotropic molecule in Salvia divinorum. Salvinorin A is considered a dissociative hallucinogen.
The dopamine receptor D4 is a dopamine D2-like G protein-coupled receptor encoded by the DRD4 gene on chromosome 11 at 11p15.5.
A dopamine agonist(DA) is a compound that activates dopamine receptors. There are two families of dopamine receptors, D1-like and D2-like. They are all G protein-coupled receptors. D1- and D5-receptors belong to the D1-like family and the D2-like family includes D2, D3 and D4 receptors. Dopamine agonists are primarily used in the treatment of the motor symptoms of Parkinson's disease, and to a lesser extent, in hyperprolactinemia and restless legs syndrome. They are also used off-label in the treatment of clinical depression. Impulse control disorders are associated with the use of dopamine agonists for whatever condition.
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.
Aporphine is an alkaloid with the chemical formula C17H17N. It is the core chemical substructure of the aporphine alkaloids, a subclass of quinoline alkaloids. It can exist in either of two enantiomeric forms, (R)-aporphine and (S)-aporphine.
Mesulergine (INNTooltip International Nonproprietary Name) (developmental code name CU-32085) is a drug of the ergoline group which was never marketed. It acts on serotonin and dopamine receptors. Specifically, it is an agonist of dopamine D2-like receptors and serotonin 5-HT6 receptors and an antagonist of serotonin 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT7 receptors.. It also has affinity for the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1F, and 5-HT5A receptors. The compound had entered clinical trials for the treatment of Parkinson's disease; however, further development was halted due to adverse histological abnormalities in rats. It was also investigated for the treatment of hyperprolactinemia (high prolactin levels).
SB-277,011A is a drug which acts as a potent and selective dopamine D3 receptor antagonist, which is around 80-100x selective for D3 over D2, and lacks any partial agonist activity.
Dopamine receptor D1, also known as DRD1. It is one of the two types of D1-like receptor family — receptors D1 and D5. It is a protein that in humans is encoded by the DRD1 gene.
Dopamine receptor D3 is a protein that in humans is encoded by the DRD3 gene.
N-n-Propylnorapomorphine (NPA) is an aporphine derivative dopamine agonist closely related to apomorphine. In rodents it has been shown to produce hyperactivity, stereotypy, hypothermia, antinociception, and penile erection, among other effects. Notably, its effects on locomotion are biphasic, with low doses producing inhibition and catalepsy and high doses resulting in enhancement of activity. This is likely due to preferential activation of D2/D3 autoreceptors versus postsynaptic receptors, the latter of which overcomes the former to increase postsynaptic dopaminergic signaling only with high doses.
SKF-83,959, a synthetic benzazepine derivative used in scientific research, acts as an agonist at the D1–D2 dopamine receptor heteromer. It behaves as a full agonist at the D1 protomer and a high-affinity partial agonist at the D2 protomer. It was further shown to act as an allosteric modulator of the sigma-1 receptor. SKF-83,959 additionally inhibits sodium channels as well as delayed rectifier potassium channels. SKF-83,959 is a racemate that consists of the R-(+)- and S-(−)-enantiomers MCL-202 and MCL-201, respectively.
6-Br-APB is a synthetic compound that acts as a selective D1 agonist, with the (R)-enantiomer being a potent full agonist, while the (S) enantiomer retains its D1 selectivity but is a weak partial agonist. (R)-6-Br-APB and similar D1-selective full agonists like SKF-81,297 and SKF-82,958 produce characteristic anorectic effects, stereotyped behaviour and self-administration in animals, with a similar but not identical profile to that of dopaminergic stimulants such as amphetamine.
7-OH-DPAT is a synthetic compound that acts as a dopamine receptor agonist with reasonable selectivity for the D3 receptor subtype, and low affinity for serotonin receptors, unlike its structural isomer 8-OH-DPAT. 7-OH-DPAT is self-administered in several animal models, and is used to study its addiction effects to cocaine.
A-86929 is a synthetic compound that acts as a selective dopamine receptor D1 agonist. It was developed as a possible treatment for Parkinson's disease, as well as for other applications such as treatment of cocaine addiction, but while it had reasonable efficacy in humans it also caused dyskinesias and has not been continued. It has mainly been used as its diacetate ester prodrug adrogolide (ABT-431), which has better bioavailability.
Dinapsoline is a drug developed for the treatment of Parkinson's disease, that acts as a selective full agonist at the dopamine D1 receptor.
Arylcyclohexylamines, also known as arylcyclohexamines or arylcyclohexanamines, are a chemical class of pharmaceutical, designer, and experimental drugs.
2-OH-NPA is a drug used in scientific research which acts as a potent and selective agonist for the dopamine D2 receptor.
PD-128,907 is a drug used in scientific research which acts as a potent and selective agonist for the dopamine D2 and D3 receptors. It is used for studying the role of these receptors in the brain, in roles such as inhibitory autoreceptors that act to limit further dopamine release, as well as release of other neurotransmitters. In animal studies, it has been shown to reduce toxicity from cocaine overdose.
Roxindole (EMD-49,980) is a dopaminergic and serotonergic drug which was originally developed by Merck KGaA for the treatment of schizophrenia. In clinical trials its antipsychotic efficacy was only modest but it was unexpectedly found to produce potent and rapid antidepressant and anxiolytic effects. As a result, roxindole was further researched for the treatment of depression instead. It has also been investigated as a therapy for Parkinson's disease and prolactinoma.
Clorotepine, also known as octoclothepin or octoclothepine, is an antipsychotic of the tricyclic group which was derived from perathiepin in 1965 and marketed in the Czech Republic by Spofa in or around 1971 for the treatment of schizophrenic psychosis.
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