Also see this explanation of the chemical basis is schizophrenia for context
The types of antipsychotics are as follows:
- Typical antipsychotics (dopamine antagonists)
- Atypical antipsychotics (5-HT2A Antagonist)
- Muscinaric agonists
In short, haloperidol, clozapine, and xanomeline reduce positive symptoms of schizophrenia and clozapine and xanomeline reduce the negative effects of schizophrenia
Typical anti-psychotics
These antagonise the D2 receptor family, and Increases the effect of dopamine.
The D1 receptor family is composed of the D1 and D5 receptors and is excitatory. The D2 receptor family is composed of the D2 through to D4 receptors and is inhibitory. G Proteins coupled to the D2 receptors family leads to decrease in cAMP and overall inhibition. The D1 receptor does the opposite.
Haloperidol is our core drug list example of a typical antipsychotic and therefore blocks dopamine D2 receptors. This works to lower the positive symptoms of schizophrenia.
Haloperidol is used when 2nd generation antipsychotics are uneffective and have a large side effect profile including: extrapyramidal side effects, parkinsons like symptoms, and anhedonia.
Additionally inhibitions of dopamine receptors in the PFC can lead to negative symptoms of schizophrenia. Weight gain and anticholinergic side effects can be seen, as haloperidol is also a mAChR antagonist. (reduced parasympathetic activity)
Atypical Antipsychotics
These are second generation antipsychotics, which are antagonists at someor all of the dopamine 2 family receptors and or 5-HT2A receptors.
Our Core drug for atypical antipsychotics is clozapine. It is an antagonist at serotonin 5-HT2A receptors and the D4 receptors. It can improve the negative symptoms of schizophrenia and has a lower risk of parkinsons like symptoms. High doses can have similar side effects to typical anti-psychotics.
Clozapine is not a first line treatment due to side effects. It has a 3.8% risk fo neutropaenia and agranulocytosis (which is fatal in 0.01% of cases.)
Clozapine is also an adrengergic α1 receptors which means decrease in blood pressure. It can cause weight gain, constipation and sedation.
Clozapine has the highest efficacy of antipsychotic drugs
Muscarinic agonists
If a mAChR antagonist like hyoscine can cause psychotic like effects, it is theorised that a mAChR agonist, like Xanomeline, could work.
Xanomeline is a muscarinic M1 and M4 partial agonist and it has been found effective.
However due to ACh being a widely used NT it has many undesirable systemic effects. Therefore it is delivered with trospium, a muscarinic antagonist which does not cross the blood brain barrier thus reducing the change of the drug everywhere but the body.
The proposed mechanism for this is that (not to be memorised again) somehow muscarinic receptors downregulate and upregulate dopamine release where needed when needed depending on the subtype