How to read a bloom

Every psychiatric drug touches a handful of targets in the brain, some hard and some barely, some to switch them on and some to switch them off. A bloom draws that handful as one flower. Here is what the petals mean, how to read one in five seconds, and a tour of the medicine cabinet, class by class, with ninety-five of them to play with.

By Reid Robison, MD. 2,220 words, with the whole garden up top, an anatomy lesson you can step through, a name-that-bloom game, nine class galleries, and a side-by-side comparer. Every bloom opens its page in the Psychiatry Wiki.

Pharmacology textbooks describe a drug as a list: binds the serotonin transporter with high affinity, blocks histamine H1, weak antagonist at alpha-1, and so on for a paragraph. The list is accurate and nobody can hold it in their head. When I was teaching this to coordinators at my research site I kept drawing the same picture on the whiteboard, a dot for the drug and a spoke for each thing it touched, longer for the targets it held tightly. After a few months the spokes had become petals, the petals had colors, and the pictures had a name.¹² This post is the field guide.

1Anatomy of a bloom

Step through one. The bloom on the left changes to whichever drug makes the point best; the text on the right says what to look at.

2The colors

Fourteen systems, one color each. The first five do most of the work in psychiatry; the rest appear on a few blooms and explain a lot of side effects.

3Name that bloom

The fastest way to learn the grammar is to guess. Six rounds; the bloom is unlabeled; the center abbreviation is hidden. Use the colors, the fills and the petal count.

4The tour, class by class

Each gallery is a drug class. Blooms animate in as you scroll; hover a petal for its note; tap a bloom to open its wiki page, where the targets are listed in a table with the chapter it belongs to.

The one-petal flowers: SSRIs

A selective serotonin reuptake inhibitor does one thing: it blocks the serotonin transporter (SERT), so a single long hollow teal petal. The small differences between members of the class are the small extra petals. Fluoxetine's 5-HT2C antagonism is why it feels activating; paroxetine's muscarinic petal is why it causes dry mouth and is harder to stop; sertraline's faint dopamine petal is a conversation-starter and probably not much more. Escitalopram is the class drawn as a single line.

Two petals, and the ones that break the pattern: SNRIs, bupropion, and the atypicals

Add a norepinephrine petal and you have an SNRI; duloxetine's is longer than venlafaxine's, which only recruits NET at higher doses. Bupropion has no serotonin petal at all, which is the whole reason it has no sexual or weight side effects. Then the odd ones: mirtazapine is all hollow petals in four colors (it blocks things, including the histamine receptor that makes it a sleep aid), trazodone's H1 petal is why a tenth of the antidepressant dose became a hypnotic, vortioxetine is five shades of serotonin with every fill type on one flower, and agomelatine is the only antidepressant whose longest petal is melatonin-colored.³

The bushes: tricyclics and MAO inhibitors

Before selectivity there were the tricyclics, and the bloom shows why they work and why they are hard to take: six petals in five colors, with histamine, muscarinic and alpha-1 blockade riding along with the reuptake block, plus a sodium-channel petal that is the cardiac risk in overdose. Nortriptyline is the cleaner member; clomipramine's long SERT petal is why it is the tricyclic for OCD. The MAO inhibitors are a different grammar entirely: grey enzyme petals, because they do not touch a receptor at all, they stop the enzyme that clears three neurotransmitters at once.

Hollow versus filled: stimulants and the non-stimulants

Here the fill rule earns its keep. Methylphenidate and amphetamine look alike, two petals in pink and orange, until you notice that methylphenidate's are hollow (it blocks the transporters) and amphetamine's are filled (it reverses them, pushing dopamine out). Same targets, opposite verbs, and the difference between a blocker and a releaser is most of the difference between the two drugs. The non-stimulants are instructive by absence: atomoxetine has no dopamine petal, and guanfacine has a single filled orange petal at a receptor rather than a transporter, which is how a drug with no stimulant properties can sharpen attention. Caffeine is here as a reminder that the most used psychoactive drug on earth works by lifting a brake (blocking adenosine), not pressing an accelerator.

From a spear to a shrub: antipsychotics

Haloperidol is a spear: one long hollow pink petal at D2 and almost nothing else, which is both its potency and its movement side effects. Chlorpromazine, the first antipsychotic, is a shrub, and every extra petal is a side effect you can name. The second generation added a long teal 5-HT2A petal in front of the D2 one. Olanzapine and clozapine are the busiest blooms on the page, and the histamine and muscarinic petals are their weight gain and their dry mouth. Quetiapine's D2 petal is short, which is why low doses are a sleep aid and not an antipsychotic. Then the third generation, and the half-filled petal: aripiprazole and cariprazine are partial agonists at D2, dimmers rather than off switches, and the bloom is the clearest way I know to show a patient what that means.

Filled teal: psychedelics and entactogens

The classic psychedelics are filled teal petals, because they are serotonin agonists, and the longest one is 5-HT2A, the receptor that makes a psychedelic a psychedelic.⁴ Psilocybin, LSD and DMT differ at the edges: LSD adds a half-filled dopamine petal, DMT a sigma petal, and 5-MeO-DMT swaps the order so that 5-HT1A leads, which is a different experience. MDMA is the mirror image of an SSRI: the same transporter, SERT, but filled, because it releases serotonin rather than blocking its reuptake. Methylone is MDMA's lighter sibling. Ibogaine is the strangest bloom in the garden, five systems in five colors, and nobody fully knows which petal does what.

Blue: the dissociatives

Ketamine is a long hollow blue petal, an NMDA glutamate-receptor blocker, with small petals for the channels and receptors that account for its other effects.⁵ Esketamine is the same flower with the left-handed half of the molecule removed; I wrote the long version in Ketamine and Spravato, explained. PCP and dextromethorphan share the blue petal and add others, and nitrous oxide is the same idea delivered as a gas.

Green: the GABA drugs

Everything that sedates, calms or puts you to sleep is in this gallery, and nearly every petal is green and filled, because these drugs enhance the brain's main inhibitory receptor rather than binding a target of their own. The differences are in which subunits: a benzodiazepine touches all of them (sedation, anxiolysis, muscle relaxation, amnesia on one flower), zolpidem leans almost entirely on alpha-1 (sleep, with less of the rest), and zuranolone reaches the extrasynaptic receptors the benzodiazepines miss.⁶ Alcohol is here too, and its bloom is the honest one: five systems, because ethanol is not selective about anything. Gabapentin is the odd flower out, a single ion-channel petal that has nothing to do with GABA despite the name.

Grey and slate: the mood stabilizers

Lithium has no receptor. Its petals are grey because its targets are enzymes inside the cell, and the bloom is a reminder that the oldest drug in psychiatry still works by a mechanism we describe rather than understand.⁷ Lamotrigine is a single sodium-channel petal; valproate spreads across GABA, sodium channels and an enzyme that edits gene expression. Three drugs, three grammars, one indication.

5Compare any two

Put two blooms side by side. The list underneath says what they share and where they part.

6What a bloom cannot tell you

A bloom is a binding diagram, and binding is only the first step of pharmacology. Five things it leaves out, which is why no bloom on this site is a prescribing guide.

• Dose. The petals are relative within one flower: the longest is that drug's tightest target. They say nothing about how many milligrams you need, and a short petal can matter at a high dose (venlafaxine's NET, quetiapine's D2) while a long one is irrelevant if the drug never reaches the brain.
• Affinity is not efficacy. How hard a drug grips a receptor and what it does once there are different numbers, and the fill color is a simplification of the second.⁸ "Partial agonist" hides a range, and a drug can be an agonist for one signaling pathway and an antagonist for another at the same receptor, which pharmacologists call functional selectivity and the bloom cannot draw.⁹
• Time. Nothing about half-life, onset, active metabolites, or the weeks it takes an antidepressant to work, which is downstream of the binding and is where the interesting biology is.
• Where in the brain. A D2 petal is a D2 petal whether the receptor is in the striatum (movement) or the mesolimbic pathway (psychosis). Location is most of the story and none of the picture.
• The person. Genetics, other medications, age, liver enzymes, and whatever else is true of the human in the chair. I wrote about that in One size fits few.

What a bloom is good for is the thing the list was bad at: holding a drug's whole profile in one glance, seeing at once why two drugs in the same class feel different, and giving a patient a picture they can point at when they ask why a sleep aid gave them a dry mouth. The affinities come from the public binding databases and from the pharmacology literature, rounded and ranked.¹⁰¹¹ Where I have had to choose between sources I have said so in the petal's note, and the wiki page for each drug has the longer version.

Educational only. The blooms simplify binding data for teaching and are not a guide to prescribing or to taking anything. Several drugs in the garden are controlled substances, investigational, or both.

References