Table 2.
Selected Serotonin Drugs Aggregated by Receptor Interactions.
| SEBM Model | Serotonin (5-HT) Receptor Sub-types | NET | MAO | Muscarinic | |||||
|---|---|---|---|---|---|---|---|---|---|
| Example Drug | 1A −1F | 2A | 2B | 2C | 3–7 | SERT | |||
| Triple Receptor (n=17) | |||||||||
| Amoxapine | 2.0 | 2.0 | 2.0 | 2.0 | 2.0 | 2.0 | ND | 2.0 | |
| Cyclobenzaprine | ND | 2.0 | 2.0 | 2.0 | 2.0 | 2.0 | ND | 2.0 | |
| Desipramine | 1.6 | 2.0 | 1.7 | 1.7 | 1.7 | 2.0 | 2.0 | ND | 1.7 |
| Meperidine | ND | ND | ND | ND | ND | 1.5 | 1.5 | ND | 1.7 |
| Paroxetine | 1.3 | ND | ND | ND | 1.3 | 2.0 | 2.0 | ND | 2.0 |
| Sertraline | ND | 2.0 | 2.0 | 2.0 | ND | 2.0 | 2.0 | ND | 2.0 |
| Duo Receptor (n=12) | |||||||||
| Fluvoxamine | ND | ND | ND | ND | ND | 2.0 | 1.1 | 1.1 | |
| Methadone | ND | 1.3 | ND | ND | ND | 1.3 | 1.3 | ND | |
| Nefazodone | 1.3 | 2.0 | 1.3 | 2.0 | ND | 2.0 | 2.0 | ND | |
| Tramadol | ND | 1.3 | 1.3 | 1.3 | ND | 2.0 | 2.0 | ND | |
| Venlafaxine | ND | 1.3 | ND | ND | ND | 2.0 | 2.0 | ND | |
| 5HT Agonists (n=8) | |||||||||
| Sumitriptan | 2.0 | 2.0 | 1.4 | 2.0 | 1.5 | ND | ND | ND | |
| Zolmitriptan | 2.0 | ND | ND | ND | 1.4 | ND | ND | ND | |
| MAOIs (n=8) | |||||||||
| Fentenyl | ND | 1.6 | ND | 1.5 | 1.5 | ND | ND | 2.0 | |
| Linezolid | ND | ND | ND | ND | ND | ND | ND | 2.0 | |
| Phenelzine | ND | ND | ND | ND | ND | ND | ND | 2.0 | |
| Mixed SERT (n=7) | |||||||||
| Granisetron | 1.6 | ND | ND | ND | 2.0 | 1.6 | ND | ND | |
| Naratriptan | 2.0 | 1.3 | ND | 1.3 | 1.3 | 1.4 | ND | ND | |
| Trazadone | 1.7 | 2.0 | 2.0 | 2.0 | 1.7 | 2.0 | ND | ND | |
|
Atypical Antipsychotics
(n=12) | |||||||||
| Olanzapine | 2.0 | 2.0 | 2.0 | 2.0 | 2.0 | 2.0 | 1.8 | ||
| Ziprasidone | 2.0 | 2.0 | ND | 2.0 | 2.0 | 2.0 | ND | ND | 2.0 |
| Miscellaneous (n=7) | |||||||||
| Buspirone | 2.0 | 2.0 | 2.0 | 2.0 | 1.5 | ND | ND | ND | |
| Lithium | ND | ND | ND | ND | ND | ND | ND | ND | |
| Valproate | ND | ND | ND | ND | ND | ND | ND | ND | |
| No known data is available to confirm bioactivity |
ND | ||||||||
| Transporter Protein Inhibition | |||||||||
| Confirmed Antagonist Activity | |||||||||
| Confirmed Agonist Activity | |||||||||
Abbreviations: SERT= Serotonin re-uptake transporter protein, NET=norepinephrine transporter protein; MAOI=monoamine oxidase inhibitors, muscarinic receptors M1 thru M5.
Receptor scores: The calculated Tanimoto score represents how well a candidate drug compares to a known interacting molecule at a specific receptor. It utilizes a continuous scale from 0 to 2.0 where a high propensity interaction is equal to 2.0 and less than 2.0 represents lower propensities. Partial activity is inferred by scores < 2.0 but an absolute threshold score for partial activity has not been clearly established.
Color coding represents confirmation of the type of activity found in a search of bioactivity and pharmacologic databases. ND denotes no bioactivity can be confirmed or inferred since no similar molecule (out of 1.5 M candidates) was identified. In other words, a receptor interaction cannot be absolutely ruled out but is considered unlikely.
A more detailed pharmacology matrix is provided in the supplemental data section and is available at http://dxulab.org/software.