Dopamine receptor, blockade

Pilowsky, LS, Costa, DC and Eli, PJ (1992) Clozapine single photon emission tomography and the D2 dopamine receptor blockade hypothesis of schizophrenia. Lancet 340 199-202. 

While FGAs exert most of their effect through dopamine receptor blockade at the dopamine (D2) receptor, the SGAs... 

Typical Versus Atypical Antipsychotics. We discussed at length in Chapter 5 just what makes a typical antipsychotic typical and what makes an atypical antipsychotic atypical. We ll spare you a rehash of that lengthy discussion however, it is important to note that all typical antipsychotics are not created equal. Although they all work by blocking the dopamine D2 receptor, their potency at this receptor varies up to 100-fold. In addition, antipsychotic side effects are not due solely to dopamine receptor blockade. In many cases, the most troublesome side effects result from blocking other receptor types including histamine, acetylcholine, and the norepinephrine alpha-1 receptor system. 

Adverse Effects. Clinically most important and therapy-limiting are ex-trapyramidal disturbances these result from dopamine receptor blockade. 

Catecholamines also appear to modulate this cortex (reviewed in Coull et ak, 2001). Studies in both monkeys and humans have found that clonidine, but not guanfacine, can impair alerting abilities in the Posner task, likely because of reducing NE release. Dopamine receptor blockade also impairs performance. 

Neuroleptic malignant syndrome (NMS) is a rare, medication-induced syndrome that may be due to dopamine receptor blockade in the basal ganglia. An altered level of consciousness, autonomic instability, hyperthermia, and severe muscular rigidity typically... 

Central nervous system Parkinson s syndrome, akathisia, dystonias Dopamine-receptor blockade... 

Endocrine system Amenorrhea-galactorrhea, infertility, impotence Dopamine-receptor blockade resulting in hyperprolactinemia... 

Most older typical antipsychotic drugs, with the exception of thioridazine, have a strong antiemetic effect. This action is due to dopamine-receptor blockade, both centrally (in the chemoreceptor trigger zone of the medulla) and peripherally (on receptors in the stomach). Some drugs, such as prochlorperazine and benzquinamide, are promoted solely as antiemetics. 

Substituted benzamides include metodopramide (discussed previously) and trimethobenzamide. Their primary mechanism of antiemetic action is believed to be dopamine-receptor blockade. Trimethobenzamide also has weak antihistaminic activity. For prevention and treatment of nausea and vomiting, metodopramide may be given in the relatively high dosage of 10-20 mg orally or intravenously every 6 hours. The usual dose of trimethobenzamide is 250 mg orally, 200 mg rectally, or 200 mg by intramuscular injection. The principal adverse effects of these central dopamine antagonists are extrapyramidal restlessness, dystonias, and parkinsonian symptoms. 

Eichler, A. J., S. M. Antelman, and A. E. Fisher. 1976. "Self-Stimulation Site-Specific Tolerance to Chronic Dopamine Receptor Blockade." Society for Neuroscience Abstracts 2 440. 

In a manner similar to that observed following treatment with antidepressant drugs, the side effects of dopamine receptor blockade occur rather quickly but the clinical benefits require 2 to 3 weeks, or more, to fully develop. This also implies that compensatory changes in brain function are required for these drugs to produce clinical benefits in psychotic patients. These changes most likely require the activation or inactivation of... 

Consequently, antipsychotic drugs all share a basic mechanism of action that involves dopamine receptor blockade. It is apparent, however, that they are not all equal in their ability to affect specific sub-types of dopamine receptors, and that their effectiveness and side effects are related to their affinity and preference for certain receptors. As indicated earlier, other neurotransmitters may also be involved in the pathogenesis of psychosis, and differences in specific antipsychotic medications may be related to their ability to directly or indirectly affect these other transmitters as well as block dopamine influence. Future studies will continue to clarify how current antipsychotics exert their beneficial effects and how new agents can be developed to be more selective in their effects on dopamine and other neurotransmitter pathways. 

Substituted benzamides include metoclopramide and trimethobenzamide. Their primary mechanism of antiemetic action is believed to be dopamine-receptor blockade. Trimethobenzamide... 

All antipsychotics + L-dopa — decreased therapeutic effect of L-dopa due to dopamine receptor blockade. 

Arnt, J. 1982, Pharmacological specificity of conditioned avoidance response inhibition in rats inhibition by neuroleptics and correlation to dopamine receptor blockade, Acta Pharmacol.Toxicol.(Copenh), vol. 51, no. 4, pp. 321-329. 

Rossum J.M.Van 1966, The significance of dopamine receptor blockade for the action of neuroleptic drugs, in Neuro-psycho-pharmacology, H. Brill, ed., Excerpta Medica Foundation, Amsterdam, pp. 321-329. 

Tripanichkul W, Stanic D, Drago J, Finkelstein DI, Horne MK (2003) D2 Dopamine receptor blockade results in sprouting of DA axons in the intact animal but prevents sprouting following nigral lesions. Eur J Neurosci 77 1033-1045. 

Acquas E, Carboni E, Leone P, Di Chiara G (1989) SCH 23390 blocks drug-conditioned place preference and place-aversion anhedonia (lack of reward) or apathy (lack of motivation) after dopamine-receptor blockade. 

Brown ZW, Gill K, Abitbol M, Amit A (1982) Lack of effect of dopamine receptor blockade on voluntary ethanol consumption in rats. Behav Neural Biol 36 291-294. 

Horvitz JC, Ettenberg A (1991) Conditioned incentive properties of a food-paired conditioned stimulus remain intact during dopamine receptor blockade. Behav Neurosci 703 536-541. 

Pierre PJ, Vezina P (1998) D1 dopamine receptor blockade prevents the facilitation of amphetamine self-administration induced by prior exposure to the drug. Psychopharmacology 735(2) 159-166. 

Rolls ET, Rolls BJ, Kelly PH, Shaw SG, Wood RJ, Dale R (1974) The relative attenuation of self-stimulation, eating and drinking produced by dopamine receptor blockade. Psychopharmacologia 38 219-230... 

Tombaugh TN, Anisman H, Tombaugh J (1980) Extinction and dopamine receptor blockade after intermittent reinforcement training failure to observe functional equivalence. Psychopharmacology 70 19-28. 

Tombaugh TN, Szostak C, Voorneveld P, Tombaugh JW (1982) Failure to obtain functional equivalence between dopamine receptor blockade and extinction evidence supporting a sensory-motor conditioning hypothesis. Pharmacol Biochem Behav 76 67-72. 

Setlow B, McGaugh JL (2000) D2 dopamine receptor blockade immediately post-training enhances retention in hidden and visible platform versions of the water image. Learning and Memory 7 187-191. 

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