The recent outbreak of the corona virus disease (COVID-19) has had major global impact. The relationship between severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection and psychiatric diseases is of great concern, with an evident link between corona virus infections and various central and peripheral nervous system manifestations. Unmitigated neuro-inflammation has been noted to underlie not only the severe respiratory complications of the disease but is also present in a range of neuro-psychiatric illnesses. Several neurological and psychiatric disorders are characterized by immune-inflammatory states, while treatments for these disorders have distinct anti-inflammatory properties and effects. With inflammation being a common contributing factor in SARS-CoV-2, as well as psychiatric disorders, treatment of either condition may affect disease progression of the other or alter response to pharmacological treatment. In this review, we elucidate how viral infections could affect pre-existing psychiatric conditions and how pharmacological treatments of these conditions may affect overall progress and outcome in the treatment of SARS-CoV-2. We address whether any treatment-induced benefits and potential adverse effects may ultimately affect the overall treatment approach, considering the underlying dysregulated neuro-inflammatory processes and potential drug interactions. Finally, we suggest adjunctive treatment options for SARS-CoV-2-associated neuro-psychiatric symptoms.

L-Dopa, the metabolic precursor of dopamine, is the treatment of choice for the symptomatic relief of the advanced stages of Parkinson’s disease. The oral bioavailability of l-dopa, however, is only about 10% to 30%, and less than 1% of the oral dose is estimated to reach the brain unchanged. l-Dopa’s physicochemical properties are responsible for its poor bioavailability, short half-life and the wide range of inter- and intrapatient variations of plasma levels. An l-dopa–lazabemide prodrug is proposed to overcome the problems associated with l-dopa absorption. Lazabemide is a monoamine oxidase (MAO)-B inhibitor, a class of compounds that slows the depletion of dopamine stores in Parkinson’s disease and elevates dopamine levels produced by exogenously administered l-dopa. l-Dopa was linked at the carboxylate with the primary aminyl functional group of lazabemide via an amide, a strategy which is anticipated to protect l-dopa against peripheral decarboxylation and possibly also enhance the membrane permeability of the prodrug. Selected physicochemical and biochemical properties of the prodrug were determined and included lipophilicity (logD), solubility, passive diffusion permeability, pK_a, chemical and metabolic stability as well as cytotoxicity. Although oral and i.p. treatment of mice with the prodrug did not result in enhanced striatal dopamine levels, 3,4-dihydroxyphenylacetic acid (DOPAC) levels were significantly depressed compared to saline, l-dopa and carbidopa/l-dopa treatment. Based on the results, further preclinical evaluation of the l-dopa–lazabemide prodrug should be undertaken with the aim of discovering prodrugs that may be advanced to the clinical stages of development.

White rhinoceros are a sentinel species for important ecosystems in southern Africa. Their conservation requires active management of their population, which, in turn, requires immobilization of individuals with an ultra-potent opioid such as etorphine. Unfortunately, when immobilized with etorphine, they develop severe hypoxaemia that may contribute to morbidity and mortality. We hypothesized that (i) etorphine causes sympathetic upregulation that is responsible for physiological complications that produce hypoxaemia and (ii) butorphanol, a partial μ opioid agonist, mitigates sympathetic upregulation, thereby improving arterial oxygen content (CaO2) and delivery (DO2). Six subadult male white rhinoceros were administered two treatments in random order: etorphine-saline (ES) and etorphine-butorphanol (EB). After intramuscular etorphine (~2.6 μg kg−1), rhinoceros became recumbent (time 0 min [t0]) and were instrumented. Baseline data were collected at t30, butorphanol (0.026 mg/kg) or 0.9% saline was administered intravenously at t37, and data were collected again at t40 and t50. At baseline, plasma noradrenaline concentration was >40 ng ml−1, approximately twice that of non-immobilized rhinoceros (t test, P < 0.05); cardiac output (Qt, by thermodilution) and metabolic rate (VO2, by spirometry/indirect calorimetry) were greater than predicted allometrically (t test, P < 0.05), and pulmonary hypertension was present. After butorphanol, noradrenaline concentration remained greater than in non-immobilized rhinoceros; in EB, CaO2 was greater, while Qt, DO2, VO2, and pulmonary pressures were less than in ES (linear mixed effect model, all P < 0.05). Increased noradrenaline concentration with increased Qt and hypermetabolism supports etorphine-induced sympathetic upregulation. Butorphanol partly attenuated these effects, increasing CaO2 but reducing Qt and, thus, DO2. Since plasma noradrenaline concentration remained increased after butorphanol administration while Qt, DO2, and VO2 decreased, a pathway independent of plasma noradrenaline concentration might contribute to the cardiopulmonary and hypermetabolic effects of etorphine. Developing treatments to combat this sympathomimesis could reduce capture-related morbidity in white rhinoceros.