Table 2. Pharmacologic Targets for Reversing the Effects of Inflammation on the Brain and Behavior.

(1) Immunotherapeutic strategies

(a) mAbs to cytokinesa,b, cytokine receptors, adhesion molecules, and B cells

(b) COX-2/prostaglandin inhibitors (eg, celecoxib)a

(c) Microglial inhibitors (eg, minocycline)a

(d) Treg enhancers (eg, Helminth ova)b

(e) Stem cell therapies (MSCs)a

(f) p38 MAPK inhibitors

(g) JAK/STAT inhibitors

(h) Phosphodiesterase type IV inhibitors

(2) Monoaminergic drugs

(a) Dopaminergic

(i) Synthesis

(1) Sapropterinb

(2) L-methylfolateb

(3) SAMe

(4) L-DOPA

(ii) Release/reuptake/metabolism

(1) Bupropionb

(2) Stimulants (eg, amphetamines, methylphenidate, modafinil)b

(3) MAOIs (eg, selegiline)b

(4) KAT inhibitors

(iii) Agonists

(1) Pramipexoleb

(2) Adenosine A (2A) receptor antagonistsb

(b) Glutamatergic

(i) Reuptake enhancers (eg, riluzole)b

(ii) Antagonists (eg, memantine, ketamine)b

(iii) IDO inhibitors (eg, 1-MT)b

(iv) KMO inhibitors

(3) Neuroendocrine mediators

(a) Glucocorticoid agonists (eg, dexamethasone)

(b) Catecholamine antagonists (eg, propranolol)

(c) Acetylcholine α 7 nicotinic agonists (also relevant to dopamine release)b

(4) Supplements/nutraceuticals

(a) Omega-3 PUFAs

(i) Eicosapentaenoic acid (EPA)a

(b) Antioxidants

(i) N-acetyl-cysteinea

Abbrevations: 1-MT: 1-methyl-tryptophan; COX-2: cyclooxygenase-2; IDO: indoleamine 2,3 dioxygenase; JAK: Janus-activated kinase; KAT: kynurenine aminotransferase; KMO: kynurenine 3-monooxygenase; L-DOPA: L-3,4-dihydroxyphenylalanine; mAb: monoclonal antibody; MAPK: mitogen-activated protein kinase; MSC: mesenchymal stem cell; PUFA: polyunsaturated fatty acid; SAMe: S-adenosyl methionine; MAOI: monoamine oxidase inhibitor; STAT: signal transducer and activator of transcription; Treg: T regulatory cell.

^aCurrently in clinical trials for depression or anxiety relative to the immune system.

^bHigh-value target (FDA approved or in phase II/III trials and available for clinical testing).