Pathways

Minocycline is a tetracycline antibiotic drug that is used topically to treat inflammatory lesions caused by the bacteria acne vulgaris. Similarly to other tetracyclines this drug acts by suppressing the growth of the bacteria it is acting on by inhibiting protein synthesis. Minocycline binds to the 30s subunit of the bacterial ribosome which prevents aminoacyl-tRNA from binding to the A site of the mRNA ribosome complex. This prevents the protein translation process in the bacteria and therefore the protein synthesis.

Minocycline is the most acitve tetracycline antibiotic that can prevent tRNA binding to 30S ribosomal of bacteria by blocking the 30S ribosomal subunit. Its lipid-solublable property allows it can pass lipid bilayers of membrane directly. Minocycline can also pass the membrane through porin channels in bacterial membrane. Due to blocking of 30S ribosomal subunit, activity of bacterial protein synthesis will be inihibited which lead to inhitation of further growth and colonization of bacteria.

Mirabegron is a beta-3 adrenergic receptor agonist that is used to treat overactive bladder and neurogenic detrusor activity. It relaxes the smooth muscle of the bladder which expands the bladder to relieve urgency. It is an oral medication that lacks significant antimuscarinic activity to reduce adverse effects in comparison to other drugs used for overactive bladder treatment. Mirabegron can be found under the brand name Myrbetriq and allows for the relaxation of detrusor smooth muscle of the bladder during the storage phase of the urinary bladder fill-void cycle via the activation of adenylyl cyclase. Once Mirabegron is administered and it binds to the beta-3 adrenergic receptor, the G protein signalling cascade begins. The alpha and beta/gamma subunits of the G protein separate and GDP is replaced with GTP on the alpha subunit. This alpha subunit then activates adenylyl cyclase which converts ATP to cAMP. cAMP then activates protein kinase A (PKA) which in turn phosphorylates targets and inhibits MLCK through decreased calcium levels causing muscle relaxation. PKA can phosphorylate certain Gq-coupled receptors as well as phospholipase C (PLC) and thereby inhibit G protein-coupled receptor (GPCR) -PLC-mediated phosphoinositide (PI) generation, and thus calcium flux. PKA phosphorylates the inositol 1,4,5-trisphosphate (IP3) receptor to reduce its affinity for IP3 and further limit calcium mobilization. PKA phosphorylates myosin light chain kinase (MLCK) and decreases its affinity to calcium calmodulin, thus reducing activity and myosin light chain (MLC) phosphorylation. PKA also phosphorylates KCa++ channels in ASM, increasing their open-state probability (and therefore K+ efflux) and promoting hyperpolarization. Since myosine light chain kinase is not activated, Serine/threonine-protein phosphatase continues to dephosphorylate myosin LC-P, and more cannot be synthesized so myosin remains unbound from actin causing muscle relaxation. This relaxation of the smooth muscles in the bladder causes the bladder to expand to relax, making the sense of urgency for urination lesser. Some side effects of using mirabegron may include nausea, constipation, headache, and dizziness.

Mirtazapine 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. Mirtazapine 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.