Psychopharmacology - W
Psychopharmacology revolution - W
Chlorpromazine has H1, M1, and α1 receptor antagonist activity. This causes sedation, anticholinergic effects, as well as orthostatic hypotension. It also functions as a blocker of D2 receptors, although it is much weaker and less selective than haloperidol in this respect. Blockade of the D2 receptors is thought to underlie the antipsychotic effect of the typical antipsychotics. However, in the case of atypicals such as clozapine and risperidone, blockade of 5HT2A receptors are thought to also account for an important part of their pharmacology.
Minor chemical manipulations in the chemical structure of chlorpromazine was used to create novel antipsychotic agents such as thioridazine and fluoperazine.
Minor chemical manipulations in the structure of chlorpromazine led to the first tricyclic antidepressant (TCA), imipramine (Tofranil), whose structure is iminodibenzyl (dibenzazepine) based.
Imipramine was first used on agitated psychotic patients, but it was shown that in the majority of cases their condition did not improve and actually worsened slightly. However, it was noted that a few of the patients who were depressed became more animated so its use in the treatment of depression became apparent.
Due to the chemical similarity of imipramine to chlorpromazine, this agent also functions as a H1, M1, and α1 receptor antagonist. Imipramine is also known to function as a fast sodium channel blocker, which is said to account for the cardiotoxicity of this agent. The collective effect of imipramine on these receptors is not thought to contribute to its therapeutic activity in the treatment of depression, although it is believed to account for mostly all of its side effects.
The usefulness of the TCAs in treating depression is thought to stem from their ability to inhibit the uptake of the neurotransmitters serotonin (5-HT) and noradrenaline (NA). It was proposed that designing agents that were more selective for 5-HT and/or NA would lower the incidence of side effects. This in turn has led to the development/discovery of the SSRIs and SNRIs.
- Psychiatric medication
- Mental health
- Nathan Kline Institute for Psychiatric Research
The investigations into the mechanism of activity of these agents that followed their discovery led to the proposal of the "chemical imbalance" of neurotransmitters theory of mood disorders, which is supposed to account for the pathophysiology and/or pathogenesis of these states. It follows that these so-called "imbalances" can be corrected by the judicious application of appropriately selected psychotropic medication(s).
An excess of dopamine is cited as the cause of schizophrenia, whereas a deficiency of noradrenaline and serotonin were cited as the cause for depression.
The discovery of reserpine was also of great significance to the development of the monoamine amine theory of depression.-
selected psychotropic medication(s)
various anticholinergic alkaloids
psychotropic drugs - W
dopamine antagonists - W
antipsychotics - W
evolutionary psychology - W regarding the relationship of self and society
psychopharmacology - GS