scholarly journals NEW 7-(2-(BENZOL[d]THIAZOL-2-YLAMINO)ETHOXY)-4-METHYL-2HCHROMEN-2-0NE DERIVATIES WITH ATYPICAL ANTIPSYCHOTIC ACTIVITY

2013 ◽  
Vol 21 (21) ◽  
pp. 97-108
Author(s):  
Gawai ASHISH ◽  
Das SANJIB ◽  
Yasbwant PATHAK
Keyword(s):  
Atypical Antipsychotic ◽  
Dopamine D2 Receptor ◽  
Analytical Data ◽  
D2 Receptor ◽  
Antipsychotic Agents ◽  
Antagonistic Activity ◽  
High Potency ◽  
Climbing Behavior ◽  
Head Twitches ◽  
Antipsychotic Activity

A new series of 7-(2-(benzo[d]thiazol-2-ylamino)ethoxy)-4-methyl-2H-chromen-2-one derivatives(4a4k) was synthesized and evaluated for their D2 and 51HT2 antagonistic activity as a measure of atypical antipsychotic properly. Compounds 7-(2-(benzo[d]thiazo/-2-ylamino)ethoxy)-4-methyl-2H-chromen-2- one derivatives (4a-4k) was synthesized by refluxing 2-amino benzothiazoles substituted derivatives (3a3k) and 7-(2-Chloroethoxy)-4-melhyl-2H-chromen-2-one (2) in dry pyridine. The synthesized compounds were characterized with the help of spectral and analytical data. Most of these compounds showed dopamine D2 receptor antagonistic activity from moderate to high potency along with serotonin 5-HT2 receptor blockage activity: a property that has been suggested to be necessary for the atypical nature of antipsychotic agents. The D2 and 5-HT2 receptor blockage activity was evaluated by inhibition of apomorphine-induced climbing behavior and 5HTP induced head twitches in mice respectively.

scholarly journals Synthesis, Computational Studies and Preliminary Pharmacological Evaluation of New Arylpiperazines

2011 ◽  
Vol 8 (3) ◽  
pp. 1044-1051
Author(s):  
Sushil Kumar ◽  
A. K. Wahi ◽  
Ranjit Singh
Keyword(s):  
Atypical Antipsychotic ◽  
Computational Studies ◽  
Lead Compound ◽  
Physiochemical Properties ◽  
Pharmacological Evaluation ◽  
Climbing Behavior ◽  
Head Twitches ◽  
Antipsychotic Activity ◽  
Albino Mice ◽  
Software Programs

A series of novel arylpiperazines were synthesized and the target compounds evaluated for atypical antipsychotic activity in apomorphine induced climbing behavior (D2antagonism), 5-HTP induced head twitches (5-HT2Aantagonism) and catalepsy studies in albino mice. The physicochemical similarity of the target compounds with respect to standard drugs clozapine, ketanserine and risperidone was assessed by calculating from a set of physiochemical properties using software programs. The test compounds(3a-j)demonstrated good similarity values with respect to the standard drugs. Among them, compound3dhas emerged as an important lead compound showing potential atypical antipsychotic like profile.

scholarly journals High dose antipsychotic polypharmacy and dopamine partial agonists - time to rethink guidelines?

2021 ◽  
pp. 026988112110264
Author(s):  
Gavin P Reynolds
Keyword(s):  
Side Effects ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Receptor Site ◽  
Receptor Occupancy ◽  
Antipsychotic Agents ◽  
High Dose ◽  
Partial Agonists ◽  
Favourable Side Effect Profile ◽  
Different Characteristics

Guidelines for the treatment of schizophrenia limit the use of antipsychotic agents to clinically-established maximum doses. This acknowledges both the absence of additional efficacy of dopamine D2 receptor antagonists above a receptor occupancy threshold, and the increases in side effects that can occur at higher doses. These limits restrict the dosing of combinations of antipsychotics as they do single agents; drugs sharing the major antipsychotic mechanism of D2 receptor antagonism will act additively in blocking these receptors. Several newer antipsychotic drugs, including aripiprazole and cariprazine, act as partial agonists at the D2 receptor site and avoid action at several other receptors, effects at which are responsible for some non-dopaminergic adverse effects. This pharmacology imparts different characteristics to the drugs resulting often in a more favourable side effect profile. Their partial agonism, along with high affinities for the D2 receptor, also means that these drugs given adjunctively may in part replace, rather than enhance, the D2 antagonism of other antipsychotic agents. This can result in an improvement in certain side effects without loss of antipsychotic efficacy. This article makes the case for distinguishing the D2 partial agonists from antagonists in defining maximum doses of combined treatments, which would increase the options available to the prescriber, emphasising that pharmacological mechanisms need to be understood in identifying optimal treatments for psychotic illness.

2-Phenyl-4-(aminomethyl)imidazoles as Potential Antipsychotic Agents. Synthesis and Dopamine D2 Receptor Binding

1995 ◽  
Vol 38 (12) ◽  
pp. 2251-2255 ◽  
Author(s):  
Andrew Thurkauf ◽  
Alan Hutchison ◽  
John Peterson ◽  
Linda Cornfield ◽  
Robin Meade ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Antipsychotic Agents ◽  
Dopamine D2

Hyperprolactinaemic anovulation

2011 ◽  
pp. 1224-1229
Author(s):  
Julian R. E. Davis
Keyword(s):  
Acute Stress ◽  
Dopamine D2 Receptor ◽  
Treatment Options ◽  
D2 Receptor ◽  
Antipsychotic Agents ◽  
Current Treatment ◽  
Serum Prolactin ◽  
Antagonist Activity ◽  
Dopamine Agonist Therapy ◽  
Pregnancy And Lactation

Prolactin is a polypeptide hormone, named from its well-known effects to promote lactation. It is essential for successful reproduction in man and mammals, although it is known to have a wide variety of nonreproductive effects whose clinical significance remains uncertain. Hyperprolactinaemia, reflecting sustained overproduction of lactin by the pituitary, is relatively common in the population. The commonest cause is the use of drugs that have dopamine D2 receptor antagonist activity (e.g. antipsychotic agents such as phenothiazines), pregnancy and lactation are the commonest physiological causes, and short-term acute stress, such as the anxiety provoked by blood sampling, is also a frequent cause of transient rises in serum prolactin that may be misinterpreted and necessitate a second confirmatory blood sample. Pathological pituitary causes of hyperprolactinaemia may reflect a functioning pituitary prolactinoma, but in many cases no adenoma is detectable on scanning, in which case the condition is termed idiopathic or nontumoral hyperprolactinaemia. The typical clinical features that suggest hyperprolactinaemia are those of galactorrhoea and oligo-/amenorrhoea. Weight gain has been reported in hyperprolactinaemic women, as has insulin resistance. Serum prolactin levels are readily measured by most clinical biochemistry laboratories, and prolactin levels should be measured on more than one occasion, with persistent unexplained hyperprolactinaemia requiring evaluation. Patients with hyperprolactinaemia may require treatment for various reasons, including restoration of ovulatory function, maintenance of adequate oestrogenization, suppression of galactorrhoea, or reduction in size of a mass lesion. Depending on the presentation and underlying cause, there are several treatment options; the main current treatment option is dopamine agonist therapy, surgery and (rarely) radiotherapy are also used in the treatment of prolactinomas.

scholarly journals Preferential Coupling of Dopamine D2S and D2L Receptor Isoforms with Gi1 and Gi2 Proteins—In Silico Study

2020 ◽  
Vol 21 (2) ◽  
pp. 436 ◽  
Author(s):  
Justyna Żuk ◽  
Damian Bartuzi ◽  
Dariusz Matosiuk ◽  
Agnieszka A. Kaczor
Keyword(s):  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Antipsychotic Agents ◽  
Intracellular Loop ◽  
Dopamine D2 ◽  
Receptor Isoforms ◽  
In Silico Study ◽  
Third Intracellular Loop ◽  
G Protein Coupled ◽  
Insight Into

The dopamine D2 receptor belongs to rhodopsin-like G protein-coupled receptors (GPCRs) and it is an important molecular target for the treatment of many disorders, including schizophrenia and Parkinson’s disease. Here, computational methods were used to construct the full models of the dopamine D2 receptor short (D2S) and long (D2L) isoforms (differing with 29 amino acids insertion in the third intracellular loop, ICL3) and to study their coupling with Gi1 and Gi2 proteins. It was found that the D2L isoform preferentially couples with the Gi2 protein and D2S isoform with the Gi1 protein, which is in accordance with experimental data. Our findings give mechanistic insight into the interplay between isoforms of dopamine D2 receptors and Gi proteins subtypes, which is important to understand signaling by these receptors and their mediation by pharmaceuticals, in particular psychotic and antipsychotic agents.

scholarly journals Multi-Target Approach for Drug Discovery against Schizophrenia

2018 ◽  
Vol 19 (10) ◽  
pp. 3105 ◽  
Author(s):  
Magda Kondej ◽  
Piotr Stępnicki ◽  
Agnieszka A. Kaczor
Keyword(s):  
Ampa Receptors ◽  
Drug Targets ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Binding Pocket ◽  
New Drugs ◽  
Allosteric Modulators ◽  
Single Target ◽  
Antipsychotic Activity ◽  
Positive Allosteric Modulators

Polypharmacology is nowadays considered an increasingly crucial aspect in discovering new drugs as a number of original single-target drugs have been performing far behind expectations during the last ten years. In this scenario, multi-target drugs are a promising approach against polygenic diseases with complex pathomechanisms such as schizophrenia. Indeed, second generation or atypical antipsychotics target a number of aminergic G protein-coupled receptors (GPCRs) simultaneously. Novel strategies in drug design and discovery against schizophrenia focus on targets beyond the dopaminergic hypothesis of the disease and even beyond the monoamine GPCRs. In particular these approaches concern proteins involved in glutamatergic and cholinergic neurotransmission, challenging the concept of antipsychotic activity without dopamine D2 receptor involvement. Potentially interesting compounds include ligands interacting with glycine modulatory binding pocket on N-methyl-d-aspartate (NMDA) receptors, positive allosteric modulators of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, positive allosteric modulators of metabotropic glutamatergic receptors, agonists and positive allosteric modulators of α7 nicotinic receptors, as well as muscarinic receptor agonists. In this review we discuss classical and novel drug targets for schizophrenia, cover benefits and limitations of current strategies to design multi-target drugs and show examples of multi-target ligands as antipsychotics, including marketed drugs, substances in clinical trials, and other investigational compounds.

scholarly journals Dopamine agonists and antipsychotics

2020 ◽  
Vol 183 (3) ◽  
pp. C11-C13
Author(s):  
Mark E Molitch
Keyword(s):  
Dopamine Receptors ◽  
Dopamine Agonists ◽  
Dopamine D2 Receptor ◽  
Rare Complication ◽  
D2 Receptor ◽  
Size Control ◽  
Antipsychotic Agents ◽  
Blocking Effect ◽  
Psychiatric Disease ◽  
Psychiatric Status

There can potentially be a number of clinical interactions that could adversely affect patient outcomes in a patient with a prolactinoma and psychiatric disease that might require antipsychotic and dopamine agonist treatment. Dopamine agonists stimulate the dopamine D2 receptor, resulting in a decrease in prolactin (PRL) levels and in prolactinoma size but action on dopamine receptors in the meso-limbic system may rarely cause psychosis and more commonly cause impulse control disorders. The psychiatric benefits of antipsychotic agents involve blocking the D2 and other dopamine receptors but this blockade often also causes hyperprolactinemia. In patients with macroprolactinomas and psychosis, observation, estrogen/progestin replacement, and surgery can be considered in addition to dopamine agonists. In those who require dopamine agonists for PRL and tumor size control, the introduction of antipsychotics may blunt this effect, so that higher doses of the dopamine agonists may be needed. Alternatively, antipsychotics that have less of a blocking effect at the D2 receptor, such as aripiprazole, can be tried, if appropriate. For patients already on antipsychotic drugs who are found to have a macroprolactinoma for which dopamine agonists are required, dopamine agonists can be initiated at low dose and the dose escalated slowly. However, such patients require careful monitoring of psychiatric status to avoid the rare complication of exacerbation of the underlying psychosis. Again, if appropriate, use of antipsychotics that have less of a blocking effect at the D2 receptor may allow lower doses of dopamine agonists to be used in this situation.

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