3 Clinical psychopharmacology3.1 General pharmacology
3.1.1 Classification major classes and intra class groups
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Written by Resident Doctor Committee · Published
Bases of classification
Basis | Example | Where it fails |
|---|---|---|
Therapeutic role | Antipsychotic, mood stabiliser | Indications overlap: antidepressants also treat pain and anxiety |
Main pharmacological action | Serotonin reuptake inhibitor | Most drugs act at several targets |
Chemical family | Phenothiazine, tricyclic, cyclopyrrolone | Close relatives behave differently in the clinic |
Duration of action | Short- or long-acting benzodiazepine | Metabolites, age and liver function alter it |
Chemical class is set by structure alone, so it is separate from generation or receptor profile.
Phenothiazines
Phenothiazines share a three-ring nucleus and divide by the side chain on the ring nitrogen.
Subgroup | Side chain | Members | Profile |
|---|---|---|---|
Aliphatic | Open carbon chain ending in a dimethylamino group | Chlorpromazine, promazine, levomepromazine | Most sedating; strong antihistaminergic and alpha-adrenergic blockade; marked postural hypotension |
Piperidine | Piperidine ring | Periciazine, thioridazine | Mainly antimuscarinic; fewest extrapyramidal effects of the phenothiazines |
Piperazine | Piperazine ring | Fluphenazine, trifluoperazine, perphenazine, prochlorperazine | Most potent; most extrapyramidal effects, least sedation |
Potency describes the dose needed, not the maximum effect.
Other antipsychotic chemical classes
Class | Members | Generation | Structural point |
|---|---|---|---|
Thioxanthene | Flupentixol, zuclopenthixol | First | Phenothiazine nucleus with a carbon at position 10 in place of the nitrogen, joined to the side chain by a double bond |
Butyrophenone | Haloperidol, droperidol, benperidol | First | No phenothiazine nucleus |
Diphenylbutylpiperidine | Pimozide | First | Two fluorophenyl rings at the end of a butyl chain carrying a piperidine |
Substituted benzamide | Sulpiride, amisulpride | Sulpiride first, amisulpride second | |
Dibenzodiazepine | Clozapine | Second | |
Thienobenzodiazepine | Olanzapine | Second | Clozapine core with one benzene ring replaced by thiophene |
Dibenzothiazepine | Quetiapine | Second | Seven-membered central ring holding one nitrogen and one sulphur |
1,2-benzisoxazole | Risperidone, paliperidone | Second | Paliperidone is the hydroxylated active metabolite of risperidone |
Quinolinone | Aripiprazole | Second |
A thioxanthene with a piperazine side chain is still not a phenothiazine, because the nucleus decides the class.
Butyrophenones are potent dopamine D2 antagonists with many extrapyramidal effects and little sedation.
First and second generation
Second-generation (atypical) status rests on a receptor profile with low extrapyramidal liability at therapeutic doses, not on chemical family.
That profile is either stronger serotonin 5-HT2A than D2 binding, or selective limbic D2 and D3 blockade.
Lurasidone and quetiapine are second-generation antipsychotics.
Sulpiride and amisulpride show the point: same benzamide family, different generations.
Antidepressants
Tricyclics
Tricyclics divide by the terminal nitrogen of the side chain: tertiary amines carry two methyl groups, secondary amines one methyl and a hydrogen.
Group | Members | Profile |
|---|---|---|
Tertiary amines | Amitriptyline, dosulepin, imipramine, clomipramine, lofepramine | Parent compounds |
Secondary amines | Nortriptyline, desipramine, protriptyline, amoxapine | N-demethylated forms of tertiary parents; lean towards noradrenaline reuptake blockade; generally better tolerated |
Lofepramine is a tertiary amine and a prodrug of the secondary amine desipramine.
Clomipramine is strongly serotonergic and effective in obsessive-compulsive disorder; the liver demethylates it to desmethylclomipramine, which blocks noradrenaline reuptake more strongly.
Other reuptake inhibitors
Selective serotonin reuptake inhibitors (SSRIs) include fluoxetine, sertraline, citalopram, escitalopram, paroxetine and fluvoxamine.
Zimeldine was the first SSRI to reach the market and was withdrawn in 1983.
Serotonin and noradrenaline reuptake inhibitors (SNRIs), venlafaxine and duloxetine, block both transporters without the tricyclic receptor profile.
Monoamine oxidase inhibitors (MAOIs)
Drug | Chemistry | Inhibition | Note |
|---|---|---|---|
Phenelzine, isocarboxazid | Hydrazine | Irreversible, A and B | Higher risk of liver injury |
Tranylcypromine | Non-hydrazine cyclopropylamine related to amfetamine | Irreversible, A and B | Stimulant effect and occasional misuse |
Moclobemide | Reversible inhibitor of monoamine oxidase A (RIMA) | Reversible, A only | Fewer dietary restrictions |
Selegiline | Irreversible, B only at low doses; A too at higher doses | Suits Parkinson's disease with little tyramine risk |
The irreversible non-selective MAOIs need tyramine precautions.
Other antidepressants
Drug | Action |
|---|---|
Trazodone | Triazolopyridine; blocks 5-HT2A receptors and weakly inhibits serotonin reuptake; sedates through H1 and alpha-1 blockade |
Mirtazapine | Blocks alpha-2, H1, 5-HT2 and 5-HT3 receptors; H1 blockade causes sedation and weight gain |
Bupropion | Inhibits noradrenaline and dopamine reuptake |
Agomelatine | Melatonin agonist and 5-HT2C antagonist |
Benzodiazepines, Z-drugs and buspirone
Benzodiazepines act at the benzodiazepine site of the gamma-aminobutyric acid type A (GABA-A) receptor and increase channel opening when GABA is present.
Drugs ending in -olam (alprazolam, triazolam, midazolam) are still benzodiazepines.
Alprazolam has a triazole ring fused to the nucleus, which groups it with triazolam and estazolam.
Long-acting diazepam and chlordiazepoxide have active metabolites that accumulate; short-acting lorazepam, temazepam and alprazolam give earlier rebound and withdrawal.
Z-drugs are not benzodiazepines but act at the same site, and their hypnotic selectivity does not remove dependence risk.
Z-drug | Chemical family | Note |
|---|---|---|
Zopiclone | Cyclopyrrolone | Eszopiclone is its active enantiomer |
Zolpidem | Imidazopyridine | |
Zaleplon | Pyrazolopyrimidine | Half-life of one hour, the shortest acting |
Buspirone is an azapirone (azaspirone) and serotonin 5-HT1A partial agonist, chemically unrelated to the benzodiazepines, with delayed onset and low dependence liability.
Other major classes
Class | Members and action |
|---|---|
Mood stabilisers | Lithium; valproate and carbamazepine are antimanic; lamotrigine prevents depressive relapse but does not treat acute mania |
Cholinesterase inhibitors | Donepezil; rivastigmine also inhibits butyrylcholinesterase; galantamine also modulates nicotinic receptors |
N-methyl-D-aspartate (NMDA) antagonist | Memantine, an uncompetitive antagonist |
Stimulants | Methylphenidate blocks dopamine and noradrenaline reuptake; amfetamines also release transmitter |
Non-stimulants for attention deficit hyperactivity disorder | Atomoxetine, a selective noradrenaline reuptake inhibitor; guanfacine, an alpha-2A agonist |