2.D,receptordecreases cAMP by inhibition of adenylate cyclaseand blocks calcium channels but opens potassiumchannelsIt is found both pre- and post-synaptically onneurons in the caudate-putamen, nucleus accumbens.and olfactory tubercle. Located in mesolimbicsystem, nigrostriatal system, area postrema on thefloor of the fourth ventricle, tubero-infundibular inhypothalamus. The activation of D, receptors causesthe increase of motor activity and stereotypedbehavior inrats
2.D2 receptor decreases cAMP by inhibition of adenylate cyclase and blocks calcium channels but opens potassium channels. It is found both pre- and post-synaptically on neurons in the caudate-putamen, nucleus accumbens, and olfactory tubercle. Located in mesolimbic system, nigrostriatal system, area postrema on the floor of the fourth ventricle, tubero-infundibular in hypothalamus. The activation of D2 receptors causes the increase of motor activity and stereotyped behavior in rats
3.D,receptorDistributed presynaptically, it belongs to D,-like receptorfamily. and is located in frontal cortex, medulla andmidbrain.4.DreceptorIt belongs to D, -like receptor family, also decrease cAMP5.D,receptorIt belongs to D, -like receptor family and is found inhippocampus and hypothalamus. D, is coded by a gene onchromosome4.All dopamine receptors have seven-transmembranedomains and are G-protein-coupled
3. D3 receptor Distributed presynaptically, it belongs to D2 -like receptor family, and is located in frontal cortex, medulla and midbrain. 4. D4 receptor It belongs to D2 -like receptor family, also decrease cAMP. 5. D5 receptor It belongs to D1 -like receptor family and is found in hippocampus and hypothalamus. D5 is coded by a gene on chromosome 4. All dopamine receptors have seven-transmembrane domains and are G-protein-coupled
Neuroleptic drugsThe neuroleptic drugs can be divided into five majorclassifications based on the structure of drugsl.Phenothiazines:chlorpromazinefluphenazinethioridazine2. Benzisoxazoles:risperidone3.Dibenzodiazepines:clozapine4haloperidolButyrophenones:5. Thioxanthenes:thiothixene
Neuroleptic drugs The neuroleptic drugs can be divided into five major classifications based on the structure of drugs. 1. Phenothiazines: chlorpromazine fluphenazine thioridazine 2. Benzisoxazoles: risperidone 3. Dibenzodiazepines: clozapine 4. Butyrophenones: haloperidol 5. Thioxanthenes: thiothixene
Mode of action1.Depamine receptor-blocking activity inbrainall of the neuroleptic drugs block dopamine receptorsin the brain and in the periphery.2.Serotonin receptor-blocking activity in brainthe newer atypical" agents appear to exert part of theirunique action through inhibition of serotonin(S)receptors.clozapine has high affinity for Dl and D4, S2,muscarinic and α-adrenergic receptors,but it is also adopamine D2 receptor antagonist.risperidone blocks S2 receptors to a greater extent thanitdoesD2receptors
Mode of action 1. Depamine receptor-blocking activity in brain all of the neuroleptic drugs block dopamine receptors in the brain and in the periphery. 2. Serotonin receptor-blocking activity in brain the newer “atypical” agents appear to exert part of their unique action through inhibition of serotonin(S) receptors. clozapine has high affinity for D1 and D4, S2, muscarinic and α-adrenergic receptors,but it is also a dopamine D2 receptor antagonist. risperidone blocks S2 receptors to a greater extent than it does D2 receptors
PhenothiazinesA.ChemistryThe phenothiazines have a three-ring structure inwhich two benzene rings are linked by a sulfur and anitrogen atom.B.Pharmacological EffectsIt is a potent dopamine receptor antagonist. It doesnot have specific selectivity between D, and Dreceptors. It is a fairly potent α-adrenergic antagonist,weak muscarinic cholinergic antagonist, weak H,antagonist and weak 5-HT, antagonist
A. Chemistry The phenothiazines have a three-ring structure in which two benzene rings are linked by a sulfur and a nitrogen atom. B. Pharmacological Effects It is a potent dopamine receptor antagonist. It does not have specific selectivity between D1 and D 2 receptors. It is a fairly potent α-adrenergic antagonist, weak muscarinic cholinergic antagonist, weak H1 antagonist and weak 5-HT2 antagonist. Phenothiazines