Introduction and definitions
The concept of therapeutic spectrum is broad and can’t be fully defined at this moment in psychopharmacology as well in general pharmacology. It refers to sometimes one or both of the following concepts
. 1) the range of beneficial clinical activities of a drug to all symptom domains of a specific diseases. Like broad spectrum anti epileptics and broad spectrum antibiotics or broad spectrum antipsychotics
. 2) The range of total clinical activities of a drug in different systems of body. Like SSRI group of drugs act as antidepressant, anti anxiety and anti obsessive at cerebral level. Anti fungal and anti microbial at immune system level. Act as epigenetic medication at epigenetic and transcription level and possibly act as anti cancer medication at the level of neoplasia
Importance of therapeutic spectrum of a drug
1) getting ideas about full therapeutic spectrum of a drug would be good to understand about possible adverse/untoward effects Like giving 5HT2A inhibitors or SSRI (5HT2A inhibitor>SSRI) in places where blood viscosity and coagulability has to be reduced.
2) The multimorbid situations where the drug can be given can be guessed from the therapeutic spectrum of the drug
Antiepileptics are invariably drugs acting in conduction system of heart and so has some reaction with anti arrhythmia drugs. SSRI and 5HT2A antagonists are good to give in IHD, mirtazapine and NASSA group is good for gastrointestinal effects
3) The different pharmacodynamic and pharmacokinetic combination of the drug can be better done if we can find the therapeutic spectrums of the drug involved
SSRI and 5HT2A antagonists good for giving with antiplatelet drugs for comorbid hyper coagulation disorders. Lithium is a good mood stabiliser for patient receiving stem cell therapy
4) The real promise of therapeutic spectrum is the broader picture. Using every systemic effect of a drug in some form or other as therapeutic effect will reduce drug crisis as well reduce the problems of adverse drug reaction.
Drugs won’t have any adverse effect then. Only different systemic beneficial effects. But that would be expecting too much for now.
Therapeutic spectrums of common psychotropic drugs, essentially incomplete because we don’t know the full extent
Antidepressant drugs
Drugs
Mechanism of action
Cerebral effects
Epigenetic effects
Immune effects
Oncological effects
Buspirone
Partial agonist 5HT1A
GAD, TRD, SSRI induced Sexual dysfunction
Can block trans placental epigenetic transmission of stress,
Increases CD4+ T cell counts, increases IL2 mRNA, increases immune responsiveness
Poorly understood anti cancer activity, needs more research
Bupropion
NE & DA reuptake inhibitor
MDD, SAD, Nicotine Dependence
ADHD (Off label)
Inhibits DNA methylation and possibly blocks histone deacetylation
Reduces pro inflammatory cytokines (TNF alpha, gamma interferon etc)
Not explored yet
Mirtazapine
NE α2, 5HT2, 5HT3 antagonist
MDD
Changes methylation and acetylation pattern of many key genes in stress
Increases CD4+ and CD8+ T cells. Decreases TNF alpha, increases IL2
Inhibits colon cancer growth in animal studies
Escitalopram
SSRI
MDD, Panic D, GAD, S anxiety D, OCD
Decreases methylation and changes hypermethylated portions back to normal
Increased innate immunity, increased T helper 2 responses, increased activity of natural killer cells, decreases TNF alpha
Inhibits tumour growth in various solid tumours
Fluoxetine
SSRI
MDD, OCD, PTSD, BDD, PMDD, Bulimia, Trichotil, Panic D
Prominent epigenetic action, epigenetic modification of caMKII alpha gene promoter. Epigenetic modification of various growth factor promoter segment. Impacts transplacental epigenetic transmission
Reduces pro inflammatory cytokines, reduces autoimmune reactions, boosts innate immunity and humoral immunity
Suppresses tumour growth, is a chemosesitizer (p glycoprotein inhibitor)
Fluvoxamine
SSRI
MDD, OCD
Same as fluoxetine
Same as fluoxetine
Same as fluoxetine
Sertraline
SSRI
MDD,OCD
Same as fluoxetin
Same as fluoxetine with antimicrobial and antifungal action
Same as fluoxetine
Amitriptyline
SNRI & 5HT2 antagonist TCA
MDD, pain
Extreme epigenetic actions. Inhibits methylation and promotes acetylation of DNA and histone at various sites.
Inhibits acid sphingomyelinase and produces leukocyte dysfunction. Reduces autoimmunity, reduces myelopeoxidase activity
Anti tumour action by inducing mitophagy and autophagy. Silences the gloomy stem cells in glioblastoma multiforme. Also is a high producer of ROS and causes oxidative damage induced anti tumour action
Nortriptyline
NRI
MDD
Same as amitriptyline
Same as amitriptyline
Same as amitriptyline
Imipramine
SNRI
MDD, Panic D, OCD
Same as amitriptyline with additional NMDA receptor gene modification action
Same as amitriptyline
Same as amitriptyline
Clomipramine
SRI & NE metabolite reuptake inhibitor
MDD, OCD, Panic D
Same as amitriptyline with additional NMDA receptor gene modification action
Same as amitriptyline
Same as amitriptyline
Venlafaxine/ DesV
SNRI
MDD, GAD, Panic D
Widespread changes in methylation and acetylation pattern in DNA and histone
Strong immunomodulatory action, specially anti inflammatory action which is greater and different from SSRI
Not explored yet.
Duloxetine
SNRI
MDD, GAD
Same as venlafaxine
Same as venlafaxine
Not much explored, have antiglioma property
Trazodone
5HT2 antagonist, 5HT1A agonist
MDD
Anti inflammatory in brain.
Same as amitriptyline
Antipsychotic drugs
Name of drug
Possible mode of action
Cerebral uses
Epigenetic aplications
Immune aplications
Malignancy application
Phenothiazine class
D2, 5HT2, M, α1, H1
Schizophrenia & other psychoses, Bipolar Mania, Hyperactivity and severe behavioral problems
None investigated yet
Strong antifungal and antimicrobial action
Direct cytotoxic agent, chemosensitizer, good adjuvant therapy in many cancer
Haloperidol
D2
Schizophrenia & other psychoses, Bipolar Mania, Tourette’s, Hyperactivity and severe behavioral problems
Promotes DNA methylation at various sites
Anti inflammatory, suppresses helper 1 T cells and possibly promotes helper 2 T cells, suppresses innate immunity
Promotes ferroptosis and direct cytotoxicity, prevents metastasis, haloperidol metabolite II prodrug in an upcoming anticancer drug
Piperazine class
D2, 5HT2
Schizophrenia & other psychoses, Bipolar Mania, Generalized anxiety
None investigated
Antimicrobial
Direct cytotoxic, growth inhibitor
Clozapine
Moderate affinity – 5HT1A/2A/ 2C/7, D2/3,
Strong – α1, M1, H1
TRS, Suicidal young people with schizophrenia
Reduces DNA methylation and even reduces hyper methylation. Increases histone acetylation, reduces genetic silencing of regenerative genes
Stimulates innate immunity and has an extensive immunomodulatory function of which we are just scratching the surface
Not much information yet
Risperidone
Strong – D2, D3, 5HT2A/7, α1
Schiz, BD
Not much known yet
Anti inflammatory and immunomodulatory
Not much is known
Olanzapine
Moderate – D2/3, 5HT2C, α1, M1; Strong – 5HT2A, H1
Schiz, BD, TRD
Mostly like clozapine but can promote methylation along with dmethylation
Anti inflammatory at high dose, promotes oligodendrosite growth
Antitumour effects in glioblastoma cells
Quetiapine
Strong – α1, H1; Moderate – 5HT2A/7, M1; Low – D2/3
Schiz, BD-M/D
Similar to olanzapine
Not explored yet
Antimetastatic in breast cancer, cytotoxic effect and growth suppression in glioma cells, suppresses glioma stem cells
Lurasidone
Strong – D2,5HT1A/7; Moderate – 5HT2A, α1
Schiz, BD-D
Can prevent epigenetic signatures of stress from developing
Anti inflammatory and immunomodulatory
Cycline dependent kinase 2 inhibitor and that makes it valuable future anticancer drug in future
Amisulpiride
Strong – 5HT1A/2A/2C, α1, H1; Moderate – D2
Schiz, BD
Not much is known yet
Not much explored
Not explored yet
Mood stabilisers
Name
Mechanism of action
Cerebral use
Epigenetic application
Immune application
Malignancy application
Lithium
Too many but primarily intracellular second messenger system stabiliser
Bipolar disorder Antidepressant augmentation Antisuicidal agent off label
Suppresses DNA methyl transferase, increases telomerase activity
Pro inflammatory As well immunomodulatory
Inhibits metastasis, inhibits tumorogenesis, is a proposed neoadjuvant therapy for glioblastoma and pancreatic carcinoma
Valproate
Histone deacetylase inhibitor, prominent epigenetic drug,
Immunomodulatory, anti inflammatory
Radiosensitizer, direct cytotoxic, inhibitor of solid tumour, useful in myelodysplastic syndrome
Conclusion
Every drug applied to body has action on genetic and epigenetic level along cellular and supra cellular level. Also all drugs have action in all systems of body. So sum total of any drug’s action on body is a combination of these actions. All of these individual actions of a drug would be beneficial in some situations and would be detrimental in some conditions. And separating these individual action by specific drug delivery system to specific area would lead to humankind getting much more benefit form their existing drug armamentarium. There is no unimodal drug in pharmacology. It’s just our knowledge that is defective and grossly inadequate.
Reference