ONE HEALTH COMPARATIVE MEDICINE, Research Topics – Adamantanes and Amantadine and more

A Literature Review and Project, Public Health Interest

Author: Jennifer Joy Brenley Nyhof

INTRODUCTION

Mechanism of Action – Adamantanes and Amantadine Section

sigma σ1 receptor agonist

dopamine D1 receptor agonist

negative allosteric modulator, nicotinic acetylcholine (AcH) receptor (nAChR)

positive allosteric modulator, dopamine D1 receptor (D1R)

NMDA (N-Methyl-D-aspartate) receptor (NMDAR) antagonist

very weak alpha-1 adrenergic receptor (α1-AR) agonist

amantadine as a phosphodiesterase inhibitor, PDEI

• PDE 1 isozyme
• calmodoulin-dependent

Amantadine and the Protective Effects of Practicing Polypharmacy

• with Amantadine, concurrent administration of:
  • angiotensin converting enzyme (ACE) inhibitor (ACEI)
    • afferent arteriole dilation, renal perfusion
    • conversely, what do we know about ACE analogues / activators / enhancers / promoters?
      • Horse (Mare, Equine) – Renin – renal excretion (urine)
        • HPLC extraction of Renin, IV infusion into human, enzyme induction, 4% increase in ACE per unit measure
  • HMG-CoA (hydroxymethylglutaryl-CoA) reductase inhibitor
    • competitive inhibition, “Statin Drug”, Statin
    • conversely, what do we know about HMG-CoA reductase analogues / activators / enhancers / promoters?
      • methylated-HMG-CoA reductase
        • ex. methyltransferase, -CH3
          • Fennec Fox species of animal (Vulpes zerda)
            • HPLC extraction of HMG-CoA reductase from urine of the Fox (similar or SAME process as described above for the extract – Horse species; the Fox excretes the highest concentration of the reductase enzyme unchanged), methyl group added in vitro to make a depot long-acting version , IV infusion (to human)
              • (Symptomatic) atherosclerosis (humans) in 4 days
              • Death (humans) in 41 days
    • Exactly what “host machinery is being hijacked” by the virus, turned intracellular factory; the virus belonging to the non-living domain?
      • Pub Med Search String Query:
        • HMG CoA reductase viral replication
          • Mohd Jaafar, F.; Monsion, B.; Belhouchet, M.; Mertens, P.P.C.; Attoui, H. Inhibition of Orbivirus Replication by Fluvastatin and Identification of the Key Elements of the Mevalonate Pathway Involved. Viruses 2021, 13, 1437. http://pmc.ncbi.nlm.nih.gov/articles/PMC8402872/pdf/viruses-13-01437.pdf
        • RNA Dependent RNA Polymerase (RdRp) enzyme diagram structure crystal +active site inhibitor +cellular repair enzyme RNA strand breaks
          • Ribavirin
          • Remdesivir
            • http://journals.sagepub.com/doi/10.1177/0018578721999804
            • http://science.org/doi/10.1126/science.abb7498
        • Neuraminidase inhibitor +oseltamivir or zanamivir

Additional Specifics of Note-Taking

• Hexamethylenetetramine
  • http://pubmed.ncbi.nlm.nih.gov/20274549
• Prazosin
  • alpha-1 adrenergic receptor (α1-AR) antagonist
  • antihypertensive
  • anti-spasmotic, urethra (decreases / reduces urethral spasm)
    • benign prostatic hyperplasia BPH
    • decreases residual urine volume (bladder), promotes voiding (urination)
    • “disorders of micturition” / “micturition disorders”
• Piperacillin Tazobactam
  • ß-lactam (beta-lactam) antibiotic
  • ß-lactamase (beta-lactamase) inhibitor