Browsing Pathways

Selegiline is an irreversible monoamine oxidase inhibitor (MAOIs). It is indicated for the initial treatment of Parkinson's disease and for adjunct therapy in patients that are having decreased response to levodopa or carbadopa. This molecule can also be used as a palliative treatment of Alzheimer's disease and at very high doses, for the treatment of depression. The monoamine oxidase is an enzyme that catalyzes the oxidative deamination of many amines like serotonin, norepinephrine, epinephrine, and dopamine. There are 2 isoforms of this protein: A and B. The first one is found in cells located in the periphery and breakdown serotonin, norepinephrine, epinephrine, dopamine, and tyramine. The second one, the B isoform, breakdowns phenylethylamine, norepinephrine, epinephrine, dopamine, and tyramine. This isoform is found in the extracellular tissues and mostly in the brain. The mechanism of action of the MAOIs is still not determined, it is thought that they act by increasing free serotonin and norepinephrine concentrations and/or by altering the concentrations of other amines in the CNS. MAO-A inhibition is thought to be more relevant to antidepressant activity than the inhibition caused by MAO B. Selective MAO B inhibitors have no antidepressant effects. MAO-B is involved in the nigrostriatal pathways, it accelerates the breakdown of dopamine in the cells. Selegiline binds selectively to MAO-B, this hinders the microsomal breakdown of dopamine, thereby amplifying the dopaminergic activities in the substantial nigra. At higher doses, selegiline can also binds MAO-A, enabling its application in depression treatment. This drug is administered as an oral tablet.

Agomelatine is structurally closely related to melatonin. Agomelatine is a potent agonist at melatonin receptors and an antagonist at serotonin-2C (5-HT2C) receptors and promotes dopamine and norepinephrine release. Agomelatine is indicated to treat major depressive episodes in adults. It is an atypical antidepressant.

Doxylamine is an ethanolamine class H1 antihistamine used to treat insomnia and allergy symptoms such as hay fever and hives. It is also used with pyridoxine in the treatment of nausea and vomiting in pregnancy. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Wakefulness is regulated by histamine in the tuberomammillary nucleus, a part of the hypothalamus. Histidine is decarboxylated into histamine in the neuron. Histamine is transported into synaptic vesicles by a monoamine transporter then released into the synapse. Normally histamine would activate the H1 histamine receptor on the post-synaptic neuron in the tuberomammillary nucleus. Doxylamine inhibits the H1 histamine receptor, preventing the depolarization of the post-synaptic neuron. This prevents the wakefulness signal from being sent to the major areas of the brain, causing sleepiness.

Distigmine is a cholinesterase inhibitor, a parasympathomimetic agent used in the treatment of neurogenic bladder dysfunction and or myasthenia gravis. This is an experimental drug that acts by inhibiting cholinesterase and also binds directly to nicotinic and muscarinic receptors in order to stimulate detrusor muscles in those who suffer from detrusor underactivity.

Phenserine is a next-generation acetylcholinesterase, used to treat dementia. It acts as a highly selective reversible acetylcholinesterase inhibitor, which is known to increase acetylcholine levels in the synaptic cleft and enhance the interaction between the neurotransmitter and the receptors. This mechanism of action is known to improve memory and cognition in alzheimer's subjects.

Netilmicin is a semisynthetic aminoglycoside that is used to treat bacterial infections within the body such as bacteremia, septicemia, respiratory tract infections, skin and soft tissue infections, burns, wounds, and peri-operative infections. It is a 1-N-ethyl derivative of sisomycin, that is similar to that of gentamicin except for the reduced ototoxicity and nephrotoxicity. Its mechanism of action is to inhibit protein synthesis by irreversibly binding to the 30S ribosomal subunit (protein S12) and interfering with the mRNA binding and acceptor tRNA sites. Due to its interference with mRNA binding and tRNA wobble base pairing this leads to misreading and early termination of peptides that are rendered nonfunctional or toxic, stunting the bacterial growth and development. It is commonly administered intramuscularly and is rapidly absorbed.

Tobramycin is an antibiotic that is commonly used to treat bacterial infections such as cystic fibrosis-associated bacterial, lower respiratory tract, urinary tract, eye, skin, and bone infections. This drug is a part of the aminoglycoside antibiotics family. It can be administered via inhalation, injection (intravenously or intramuscular), or even via topical cream. Tobramycin acts by binding to bacterial membranes causing displacement of divalent cations and increasing membrane permeability allowing entry into the bacterial cell. Once inside the bacterial cell, tobramycin then targets the bacterial 30S ribosome and binds to it, halting protein synthesis. It binds to the site where the normal base pairing of codon and anti-codon takes place as well as adding amino acids to the growing polypeptide chain, with this blocked it leads to termination of the chain and production of non-functional proteins. The adverse effects of tobramycin are not well known therefore if a patient is experiencing overdose hemodialysis should be performed to clear the excess of tobramycin as they are at risk of nephrotoxicity, ototoxicity, neuromuscular blockade, respiratory paralysis, and/or respiratory failure.

Cyclobenzaprine is a centrally acting skeletal muscle relaxant structurally related to tricyclic antidepressants. Cyclobenzaprine relieves skeletal muscle spasms of local origin without interfering with muscle function. In preclinical research, cyclobenzaprine reduced skeletal muscle hyperactivity. Research indicates that it primarily acts within the central nervous system in the brain stem. Cyclobenzaprine does not work directly on skeletal muscle or the neuromuscular junction, although an overlapping action on the spinal cord may contribute to its overall skeletal muscle relaxant activity. Evidence implies that the resultant impact of cyclobenzaprine is a decline of tonic somatic motor activity, affecting both gamma(γ) and alpha(α) motor systems. Recent research suggests that cyclobenzaprine is a (5-HT2) receptor antagonist, and this additional action is responsible for its antispasmodic effect. Cyclobenzaprine effectively improves muscle spasms, reduces local pain and tenderness, and increases the range of motion in acute, painful musculoskeletal conditions. Cyclobenzaprine is an antispasmodic drug effective in treating muscle spasms. However, cyclobenzaprine is not an antispasticity drug. Therefore, cyclobenzaprine is ineffective in treating spasticity associated with cerebral or spinal cord pathology or children with cerebral palsy.

Emicizumab also known as Hemlibra, is a humanized recombinant monoclonal antibody that mimics coagulation factor VIII and can bind to activated coagulation factor IX and X. Emicizumab performs the function of coagulation factor VIII, with the ability to also bind to both coagulation factor IX and X. It is administered subcutaneously, the antibody is metabolized through endothelial cells taking up the antibodies and degrading them into small peptides and amino acids.

Sunitinib is a chemotherapeutic agent and receptor tyrosine kinase inhibitor utilized in the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST). Approved by the US FDA on January 26, 2006, it's administered orally and operates as a multi-targeted small-molecule receptor tyrosine kinase (RTK) inhibitor. Its actions encompass inhibiting key signaling pathways by targeting various RTKs, including platelet-derived growth factor receptors (PDGF-R), vascular endothelial growth factor receptors (VEGF-R), and KIT (CD117) in GIST cases. Sunitinib also affects RET, CSF-1R, and flt3 RTKs. Indicated conditions for sunitinib include advanced RCC, adjuvant treatment post-nephrectomy for high-risk recurrent RCC, and well-differentiated pancreatic neuroendocrine tumors (pNET) with unresectable locally advanced or metastatic disease. Its mechanism entails inhibiting RTKs implicated in cancer progression, tumor growth, and angiogenesis. This inhibition encompasses PDGFRa, PDGFRb, VEGFR1, VEGFR2, VEGFR3, KIT, FLT3, CSF-1R, and RET receptors. The primary metabolite mirrors sunitinib's potency in relevant assays.