Pathways

Samarium (153Sm) lexidronam is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Samarium (153Sm) lexidronam passes through the liver and is then excreted from the body mainly through the kidney.

Samidorphan, also known as Lybalvi, is a novel opioid-system modulator, it is similar to naltrexone. It functions primarily as a μ-opioid receptor antagonist and is used primarily in combination with antipsychotics to reduce their metabolic dysfunction-associated adverse effects. Samidorphan was first approved by the FDA in May 2021. It is used in combination with olanzapine, an antipsychotic, for the treatment of bipolar disorder and for the treatment of schizophrenia in adults. It is demonstrated that the addition of samidorphan to olanzapine helps mitigate the metabolic-related adverse effects of olanzapine; presumably, this is due to opioid receptor signaling, though the exact mechanism remains to be determined. Samidorphan functions primarily as a μ-opioid receptor antagonist and as a κ/δ-opioid receptor partial agonist. Since it is an opioid antagonist, this drug can potentiate opioid withdrawal. Samidorphan acts as an antagonist at the μ-opioid, a partial agonist at both the κ- and δ-opioid receptors in vitro. Samidorphan inhibits the exchange of GTP for GDP which is required to activate the G-protein complex. This prevents the Gi subunit of the mu opioid receptor from inhibiting adenylate cyclase, which can therefore continue to catalyze ATP into cAMP. cAMP increases the excitability in spinal cord pain transmission neurons which allows the patient to feel pain rather than the analgesic effects of opioids. The inhibition of Mu-type opioid receptors also prevents the Gi subunit of the mu opioid receptor from activating the inwardly rectifying potassium channel increasing K+ conductance which would cause hyperpolarization. Samidorphan also prevents the gamma subunit of the mu opioid receptor from inhibiting the N-type calcium channels on the neuron. This allows calcium to enter the neuron and depolarize. The inhibition of mu-opioid receptors prevents hyperpolarization in the neuron, allowing it to fire at a normal rate. The neuron is able to depolarize and the high concentration of calcium releases GABA into the synapse which binds to GABA receptors. GABA receptors inhibits dopamine cell firing in the pain transmission neurons. This prevents the analgesic and depressive effects of opioids, preventing opioid overdose. GABA also inhibits dopamine cell firing in the reward pathway which is the main cause of addiction to opioids and other drugs.

Metabolites of Samidorphan are predicted with biotransformer.

Saprisartan is an Type-1 angiotensin II (AT1) receptor antagonist, its chemical structure comes from losartan. This drug is a noncompetitve antagonism of AT1. It blocks the renin-angiotensin-aldosterine system (RAAS) when binding the AT1 receptor that mediates the important actions of angiotensin II. By inhibiting those actions, saprosartan leads to a decrease in sodium reabsorpion and a decrease in vasoconstriction, those two actions decrease the blood pressure.

Saquinavir is an HIV protease inhibitor used in combination with ritonavir and other antiretroviral agents for the treatment of HIV-1 with advanced immunodeficiency. In 1995 it became the first protease inhibitor approved by the FDA, followed shortly by ritonavir in 1996, and remains in clinical use today due to a relatively benign adverse effect profile as compared to other antiretroviral therapies. While its efficacy was initially limited by exceptionally poor oral bioavailability (approximately 4%), its current indications require the co-administration of ritonavir, that increases the bioavailability and subsequent serum concentrations of saquinavir, thus dramatically improving antiviral activity. The HIV virus binds and penetrates the host cell. Viral RNA is transcribed into viral DNA via reverse transcriptase. Viral DNA enters the host nucleus and is integrated into the host DNA via integrase. The DNA is then transcribed, creating viral mRNA. Viral mRNA is translater into the gag-pol polyprotein. HIV protease is synthesized as part of the Gag-pol polyprotein, where Gag encodes for the capsid and matrix protein to form the outer protein shell, and Pol encodes for the reverse transcriptase and integrase protein to synthesize and incorporate its genome into host cells. HIV-1 protease cleaves the Gag-pol polyprotein into 66 molecular species, including HIV-1 protease, integrase, and reverse transcriptase. Saquinavir inhibits HIV-1 protease. This inhibition prevents the HIV virion from fully maturing and becoming infective. Using the lipid bilayer of the host cell, a virus is formed and released. The inhibition of HIV-1 protease prevents the necessary molecular species from forming, therefore preventing maturation and activation of viral particles. This forms immature, non-infectious viral particles, therefore, Saquinavir prevents the virus from reproducing.