The D2-like receptors include the D2, D3 and D4 receptor subtypes. Each receptor subtype has its own set of pharmacological properties with different affinities of specific drugs for each subtype. Clozapine is a D2-like selective antagonist with a broad range of pharmacological action, binding to all three D2-like receptors. However, it is 28 times more potent at the D4 receptor than the D2 receptor. Its antipsychotic effects are thought to be mediated primarily by 5-HT 2A/2C and D2 receptor antagonism. Quinpirole is a D2-like selective agonist, binding to all three D2-like receptors; no specific agonists have yet been identified for each subtype.
The D2-like receptors include the D2, D3 and D4 subtypes. Each receptor subtype has its own set of pharmacological properties with different affinities of specific drugs for each subtype. Rispiradone is a D2-like selective antagonist, binding to all three D2-like receptors. However, it has a higher affinity for the D2 receptor than for the D3 receptor. The new generation of antipsychotics, such as rispiradone, have a high affinity for the D2 receptor subtype. These differences in affinities are of clinical significance, as the antipsychotic effects of these drugs are thought to be mediated by D2 receptor antagonism.
Neuroleptic, or antipsychotic, agents are a group of drugs used to treat schizophrenia and other types of psychoses. Risperidone is a newer ‘atypical’, or ‘second-generation’, neuroleptic and is more selective than the older ‘typical’ neuroleptics. Risperidone can bind to dopamine D2, 5-HT2 and α2 adrenergic receptors in the brain. The efficacy of neuroleptics is thought to be due to antagonism of dopamine receptors in the mesolimbic and mesofrontal systems. The atypical neuroleptics, which have little or no affinity for D1 receptors, do not exhibit some of the side effects associated with D1 antagonism that the older neuroleptics have. The adverse effects associated with atypical neuroleptics, such as tachycardia, impotence and dizziness, are due to the non selective binding to α adrenoreceptors.
Neuroleptic, or antipsychotic, agents are a group of drugs used to treat schizophrenia and other types of psychoses. Haloperidol an older ‘typical’, or ‘first-generation’, neuroleptic is non-selective and binds to a broad range of receptors. It can bind to dopamine D1 and D2, 5-HT2, histamine H1 and α2 adrenergic receptors in the brain. The efficacy of neuroleptics is thought to be due to antagonism of dopamine receptors in the mesolimbic and mesofrontal systems. The adverse effects of typical neuroleptics include tachycardia, impotence and dizziness, and these unwanted effects are caused by non-selective interaction at the α adrenoreceptor. Other adverse effects include and sedation and weight gain, which is due to histamine H1 receptor blockade.
Schizophrenia is associated with increased activity in the dopaminergic system. Many antipsychotic drugs (neuroleptics) exert their therapeutic effects by D2 receptor blockade. There are 2 main categories of neuroleptics – typical (eg chlorpromazine, haloperidol) and atypical (eg clozapine, risperidone). The difference between the two types include fewer extrapyramidal side effects with atypical antipsychotics, and greater efficacy in treatment-resistant patients and against negative symptoms also with atypical antipsychotics. The neuroleptics show varying patterns of selectivity at receptor sites. Older neuroleptics such as chlorpromazine show greater affinity for D2 receptors compared with D1 receptors. Some of the newer agents (eg sulpiride) are highly selective for D2 receptors, whereas clozapine is relatively non-selective for D1 or D2, but has high affinity for D4. Important side effects common to most neuroleptics are extrapyramidal motor disturbances and endocrine disturbances (increased prolactin secretion), which are secondary to dopamine receptor antagonism. Other side effects (eg dry mouth, blurred vision, sedation, hypotension, etc.) are due to blockade of receptors such as α-adrenoceptors, muscarinic cholinergic receptors and histamine H1 receptors. Additionally, rare idiosyncratic reactions can occur; obstructive jaundice has been reported with chlorpromazine therapy, leukopenia can occur with clozapine and thioridazine has been associated with cardiac conduction defects.