Pathways

Practolol is a cardioselective beta 1 blocker. It can be administered orally, where it passes through hepatic portal circulation, and enters the bloodstream and travels to act on cardiomyocytes. In bronchial and vascular smooth muscle, practolol can compete with epinephrine for beta-2 adrenergic receptors. By competing with catecholamines for adrenergic receptors, it inhibits sympathetic stimulation of the heart. The reduction of neurotransmitters binding to beta receptor proteins in the heart inhibits adenylate cyclase type 1. Because adenylate cyclase type 1 typically activates cAMP synthesis, which in turn activates PKA production, which then activates SRC and nitric oxide synthase, its inhibition causes the inhibition of cAMP, PKA, SRC and nitric oxide synthase signaling. Following this chain of reactions, we see that the inhibition of nitric oxide synthase reduces nitric oxide production outside the cell which results in vasoconstriction. On a different end of this reaction chain, the inhibition of SRC in essence causes the activation of Caspase 3 and Caspase 9. This Caspase cascade leads to cell apoptosis. The net result of all these reactions is a decreased sympathetic effect on cardiac cells, causing the heart rate to slow and arterial blood pressure to lower; thus, practolol administration and binding reduces resting heart rate, cardiac output, afterload, blood pressure and orthostatic hypotension. By prolonging diastolic time, it can prevent re-infarction. One potentially less than desirable effect of non-selective beta blockers like practolol is the bronchoconstrictive effect exerted by antagonizing beta-2 adrenergic receptors in the lungs. Clinically, it is used to increase atrioventricular block to treat supraventricular dysrhythmias. Practolol also reduce sympathetic activity and is used to treat hypertension, angina, migraine headaches, and hypertrophic subaortic stenosis.

Pralatrexate is a folate analog, used for the treatment of peripheral T-cell lymphoma. Administered intravenously it acts to inhibit dihydrofolate reductase, specifically in cancer cells that have an overexpression of a transporter known as reduced folate carrier protein-1. This transporter is responsible for moving folate that is required for DNA synthesis and replication, without the folate the cancer cells cannot rapidly replicate. Pralatrexate also is affected by folyopolyglutamate synthase, allowing the drug to stay within the body for a longer period of time. It is eliminated via the urine and has a half-life of 12-18 hours.

Metabolites of Pralsetinib are predicted with biotransformer.

Pramipexole is indicated for the management of Parkinson's disease and symptomatic treatment of moderate to severe primary Restless Legs Syndrome (RLS). Pramipexole likely restores balance to the dopaminergic system, controlling the symptoms of this condition. Restless legs syndrome is thought to occur, in part, through dysfunction of the dopaminergic system, resulting in unpleasant lower extremity symptoms. Pramipexole is considered a non-ergot dopamine agonist that shows specificity and strong activity at the D2 subfamily of dopamine receptors in vitro, binding selectively and dopamine D2 receptors and showing a preference for the dopamine D3 receptor subtype rather than other subtypes. Pramipexole's efficacy in PD is attributed to its D3 selectivity. It binds to presynaptic dopamine autoreceptors exerting negative feedback on endogenous dopamine synthesis. This process leads to a decrease in oxidative stress, which mitigates the damage to the nigrostriatal pathways

Metabolites of Pramipexole are predicted with biotransformer.