Dopamine receptor blockers

DeWit, H., and Wise, R.A. Blockade of cocaine reinforcement in rats with the dopamine receptor blocker pimozide, but not with the noradrenergic blockers phentolamine and phenoxybenzamine. Can J Psychol 31 195-203, 1977. 

Banning, JW, Uretsky NJ, Patil PN, Beal JL. Reticuline a dopamine receptor blocker. Life Sci 1980 26 2083-2091. 

Drugs that are successful in treating the disease act as dopamine receptor blockers and are known as antipsychot-ics or neuroleptics (e.g. chlorpromazine, haloperidol). Antipsychotic drags reduce some of the symptoms, especially the delusions and hallucinations. A side-effect of the drugs is that they can result in symptoms similar to those seen in patients with Parkinson s disease. This is not surprising, since the hypothesis to explain Parkinson s disease is too low a concentration of dopamine in a specific area of the brain (see below). 

Post RM, Jimerson DC, Bunney WE, et al. Dopamine and mania behavioral and biochemical effects of the dopamine receptor blocker pimozide. Psychopharmacology 1980 67 297-305. 

Reserpine depletes cerebral dopamine by preventing intraneuronal storage (see Chapter 6) it is introduced in low doses (eg, 0.25 mg daily), and the daily dose is then built up gradually (eg, by 0.25 mg every week) until benefit occurs or adverse effects become troublesome. A daily dose of 2-5 mg is often effective in suppressing abnormal movements, but adverse effects may include hypotension, depression, sedation, diarrhea, and nasal congestion. Tetrabenazine (12.5-50 mg orally three times daily) resembles reserpine in depleting cerebral dopamine and has less troublesome adverse effects it is now available in the USA. Treatment with postsynaptic dopamine receptor blockers such as phenothiazines and... 

In our 1987 review, we summarized the research and clinical experience in this area [1], Surprisingly, in spite of the enormous public interest in medical marijuana and countless articles in the daily press and magazines focused predominantly on this aspect of marijuana use, little progress has been reported on the antiemetic activity of cannabinoids in the last decade. Plasse et al. have reviewed the clinical experience gained over 7 years with dronabinol (d9-THC) in antiemetic treatment [117]. With doses of 7 mg/m2 or below, complete response was noted in 36% of the patients, 32% showed partial response and 32% showed no response. However, 65% displayed drowsiness and dizziness and 12% had dysphoric effects. Combination treatment of dronabinol with prochlorperazine (a dopamine receptor blocker widely used as an antipsychotic drug with antiemetic effects) was more effective than each drug alone [118]. 

A disturbance in the dopaminergic neurotransmission plays a key-role in the pathogenesis of schizophrenia (Carlsson, 1988). Most di ugs amedoradng psychodc symptoms act as dopamine receptor blockers, in pardcular D2 receptor blockers. In light... 

Specific cell injury or cell functional disorder occur with individual drugs or drug classes, e.g. tardive dyskinesia (dopamine receptor blockers), retinal damage (chloroquine, phenothiazines), retroperitoneal fibrosis (methysergide), NSAIDs (nephropathy). Cancer may occur, e.g. with oestrogens (endometrium) and with immunosuppressive (anticancer) drugs. 

Interactions. With nonselective monoamine oxidase inhibitors (MAOI), the monoamine dopamine formed from levodopa is protected from destruction it accumulates and also follows the normal path of conversion to noradrenaline (norepinephrine), by dopamine (J-hydroxylase severe hypertension results. The interaction with the selective MAO-B inhibitor, selegiline, is possibly therapeutic (see below). Tricyclic antidepressants are safe. Levodopa antagonises the effects of antipsychotics (dopamine receptor blockers). Some antihypertensives enhance hypotensive effects of levodopa. Metabolites of dopamine in the urine interfere with some tests for phaeochromocytoma, and in such patients it is best to measure the plasma catecholamines directly. 

PET scans of the brain of untreated schizophrenics have revealed small increases in dopamine receptors. Dopamine receptor blockers should be avoided in parkinsonism. While most conventional antipsychotic drugs block receptors, this action is not an absolute requirement for antipsychotic action, since clozapine and newer drugs have a very low affinity for such receptors. The clinical potency of antipsychotic drugs does not correlate well with their beta adrenoceptorblocking actions. The effects of phencyclidine (PCP) closely parallel an acute schizophrenic episode, but PCP has no actions on brain dopamine receptors. The answer is (D). 

Maruiwa, F., Kim, S.D., Nao-I, N., and Sawada, A. 1992. [Effects of metoclopramide, dopamine receptor blocker, on the EOG light peak]. Nippon Ganka Gakkai Zasshi 96 375-380. 

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