Receptors neuroleptic drugs

The antipsychotic activity of neuroleptics (D2-like receptor antagonists) has led to the development of many different ligands for the D2 receptor. These drugs... 

What is obvious from all the experimental evidence is that it is easier to unravel the cause of the undesirable than it is to explain the desirable effects of neuroleptic drugs. EPSs occur because such drugs all have some D2 antagonist activity and so reduce DA transmission in the striatum. The degree to which they achieve this and whether they are typical or atypical depends on their affinity for D2 striatal receptors, since EPSs... 

Peroutka, S.J., U Prichard, D.C., Greenberg, D.A. and Snyder, S.H. (1977) Neuroleptic drug interactions with norepinephrine alpha receptor binding sites in rat brain. Neuropharmacology, 16, 549-556. 

Dopamine A few studies have examined the dopaminergic effects of LSD. The affinity of LSD for D2 receptors is similar to its affinity for 5-HT2 sites, and it has a slightly lower affininty for D1 receptors (Watts et al. 1995). LSD has partial agonist effects at D2 receptors as seen in the inhibition of prolactin release (Giacomelli et al. 1998). Neuroleptic drugs are also used clinically to terminate an LSD experience. Thus, the effects of LSD on dopaminergic function may contribute to its hallucinogeinc effects. 

Because of multiple receptor actions, which occur at different concentrations, different neuroleptics have different action profiles. There are many classifications for neuroleptic drugs, the least useful of which is probably based on their chemical structure. Other classifications include linear classifications based on the propensity to cause EPS, or multidimensional ones such as the Liege star which combines information on three positive effects (anti-autistic, antiproductive, antipsychotic), and three negative (hypotensive, extrapyramidal, sedative). In a general way, the more sedative neuroleptics such as levomepromazine, used more to treat acute agitation states, cause more hypotension related to alpha blockade, whereas those that act best on delirium (productive states) such as haloperidol tend to cause more EPS. 

Neuroleptic drugs are used in the treatment of psychosis, such as schizophrenia they are generally antagonist ligands of dopamine at the central nervous system level. " Indications and therapeutic effects of the various families of neuroleptics result from two factors. The first one is the specifity of the ligand toward the different types of dopaminergic receptors, which are unequally distributed in the... 

Peroutka, S.J. and Snyder, S.H. (1980) Relationship of neuroleptic drug effects at brain dopamine, serotonin, a-adrenergic, and histamine receptors to clinical potency. Am Psychiatry 137 1518-1522. 

It is an atypical neuroleptic drug. It interferes with binding of dopamine at D1 and D2 receptors in CNS. It produces few ex-trapyramidal symptoms. 

Dopamine is a major neurotransmitter which acts on multiple receptors. It can activate both a and 3 adrenoceptors in addition to acting on specific dopamine receptors. These are widely distributed throughout the CNS and are also present in the renal tubules and renal and mesentric blood vessels, and many dopaminergic drugs are used in the treatment of Parkinson s disease, psychiatric disorders, as antiemetics, and for renal protection. Neuroleptic drugs, such as haloperidol and droperidol, are dopamine receptor antagonists. 

The hypothetical link between dopamine and schizophrenia was forged by two reciprocally related findings. The first was that potent dopamine agonist stimulants like d-amphetamine and cocaine could cause a psychosis that was schizophrenia-like, in that it had auditory hallucinations and paranoia. The second was that the neuroleptic drugs that were effective in reversing both schizophrenia and stimulant-induced psychosis were dopamine blockers. Moreover, the antipsychotic potency of the neuroleptics was proportional to their binding affinity to the D2 receptor. 

Some patients who take clozapine take another neuroleptic drug, and the consequences of this practice in terms of prolactin have been studied in five patients (758). After the addition of haloperidol (4 mg/day) to clozapine the mean prolactin concentration increased from 9.7 ng/ml to 16 ng/ml at week 4 and 19 ng/ml at week 6. Each subject had an increase in the percentage of D2 receptor occupancy, and the group mean increased from 55% at baseline to 79% at week 4 the increased prolactin concentrations correlated with receptor occupancy. 

While there is extensive experimental evidence showing that all clinically effective neuroleptic drugs block dopamine receptors, and a general agreement that blockade of the D2 receptors in the mesocortical regions is particularly important for antipsychotic activity, only with the advent of... 

Laborit in the early 1950s is credited with the observation that chlorpromazine had a "calming effect in disturbed schizophrenic patients and since that time psychopharmacologists have sought to explain the mechanism of action of neuroleptic drugs. Carlsson and Linquist in 1963 demonstrated a link between the therapeutic effects of the phenothiazine neuroleptics and an inhibition of dopamine receptor function. This led to... 

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