Pathways

Benzatropine, known commonly as Cogentin, is an anticholinergic drug used to treat Parkinson's disease and extrapyramidal symptoms, except tardive dyskinesia. Benzatropine is used in therapy for parkinsonism, referring to a group of neurological disorders that produce symptoms such as tremors, slow movement, and stiffness. It has been determined to be a dopamine uptake inhibitor since 1970 and was approved by the FDA in 1996. Inhibiting dopamine reuptake in presynaptic carrier-mediated transport has a dose-dependent increase in the nerve terminal. Benzatropine blocks the reuptake transporters of both dopamine which prolongs their duration in the synapse so that they can bind more readily to the receptors. It is also known for its affinity for muscarinic receptors in the human brain. Benzatropine crosses the blood-brain barrier through diffusion. Dopamine is synthesized in the ventral tegmental area of the brain from tyrosine being synthesized into L-dopa by the enzyme Tyrosine 3-monooxygenase. L-Dopa is then synthesized into dopamine with the enzyme aromatic-L-amino-acid decarboxylase. Dopamine then travels to the prefrontal cortex where it is released into the synapse when the neuron is stimulated and fires. Benzatropine binds to the sodium-dependent dopamine transporter which prevents dopamine from re-entering the presynaptic neuron. The dopamine then binds to Dopamine D4 receptors on the postsynaptic membrane. The dopamine D4 receptor activates the Gi protein cascade which inhibits adenylate cyclase. This prevents adenylate cyclase from catalyzing ATP into cAMP. The low concentration of cAMP is unable to activate protein kinase A which prevents or lowers neuronal excitability. The change in dopamine corrects the imbalance between dopamine and acetylcholine in Parkinson's disease.

Metabolites of Benzethonium are predicted with biotransformer.

Benzhydrocodone is a benzylic prodrug of hydrocodone.It was developed to reduce parenteral bioavailability of the active metabolite as a deterrent of abuse.It was first approved by the FDA in February 2018 in combination with acetaminophen. Benzhydrocodone is metabolized in the liver by CYP2D6 or CYP3A4 into hydrocodone. Hydrocodone is transported to the dorsal horn of the spinal cord where it inhibits mu opioid receptors. Hydrocodone binds to mu opioid receptors on presynaptic neuron membranes, stimulating the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine, and noradrenaline is inhibited. Opioids close N-type voltage-operated calcium channels and open calcium-dependent inwardly rectifying potassium channels. This results in hyperpolarization and reduced neuronal excitability. Morphine acts at A delta and C pain fibres in the dorsal horn of the spinal cord. By decreasing neurotransmitter action there is less pain transmittance into the spinal cord. This leads to less pain perception.