The alkaloid L-(-)-scopolamine [L-(-)-hyoscine], a belladonna alkaloid, competitively inhibits muscarinic receptors for acetylcholine and acts as a nonselective muscarinic antagonist, producing both peripheral antimuscarinic properties and central sedative, antiemetic, and amnestic effects. Scopolamine acts: i) as a competitive inhibitor at postganglionic muscarinic receptor sites of the parasympathetic nervous system, and ii) on smooth muscles that respond to acetylcholine but lack cholinergic innervation. It has been suggested that scopolamine acts in the central nervous system (CNS) by blocking cholinergic transmission from the vestibular nuclei to higher centers in the CNS and from the reticular formation to the vomiting center. Scopolamine can inhibit the secretion of saliva and sweat, decrease gastrointestinal secretions and motility, cause drowsiness, dilate the pupils, increase heart rate, and depress motor function. Scopolamine is used for premedication in anesthesia and for the prevention of nausea and vomiting (post operative and associated with motion sickness).

The alkaloid L-(-)-scopolamine [L-(-)-hyoscine], a belladonna alkaloid, competitively inhibits muscarinic receptors for acetylcholine and acts as a nonselective muscarinic antagonist, producing both peripheral antimuscarinic properties and central sedative, antiemetic, and amnestic effects. Scopolamine acts: i) as a competitive inhibitor at postganglionic muscarinic receptor sites of the parasympathetic nervous system, and ii) on smooth muscles that respond to acetylcholine but lack cholinergic innervation. It has been suggested that scopolamine acts in the central nervous system (CNS) by blocking cholinergic transmission from the vestibular nuclei to higher centers in the CNS and from the reticular formation to the vomiting center. Scopolamine can inhibit the secretion of saliva and sweat, decrease gastrointestinal secretions and motility, cause drowsiness, dilate the pupils, increase heart rate, and depress motor function. Scopolamine is used for premedication in anesthesia and for the prevention of nausea and vomiting (post operative and associated with motion sickness).

Caffeine is a methylxanthine alkaloid found in the seeds, nuts, or leaves of a number of plants native to South America and East Asia that is structurally related to adenosine and acts primarily as an adenosine receptor antagonist with psychotropic and anti-inflammatory activities. Upon ingestion, caffeine binds to adenosine receptors in the central nervous system (CNS), which inhibits adenosine binding. This inhibits the adenosine-mediated downregulation of CNS activity; thus, stimulating the activity of the medullary, vagal, vasomotor, and respiratory centers in the brain. The anti-inflammatory effects of caffeine are due the nonselective competitive inhibition of phosphodiesterases. Caffeine is used by mouth or rectally in combination with painkillers (such as aspirin and acetaminophen) and a chemical called ergotamine for treating migraineheadaches. It is also used with painkillers for simple headaches and preventing and treating headaches after epidural anesthesia. Caffeine creams are applied to the skin to reduce redness and itching in dermatitis. Healthcare providers sometimes give caffeine intravenously (by IV) for headache after epidural anesthesia, breathing problems in newborns, and to increase urine flow. In foods, caffeine is used as an ingredient in soft drinks, energy drinks, and other beverages.

Caffeine is a methylxanthine alkaloid found in the seeds, nuts, or leaves of a number of plants native to South America and East Asia that is structurally related to adenosine and acts primarily as an adenosine receptor antagonist with psychotropic and anti-inflammatory activities. Upon ingestion, caffeine binds to adenosine receptors in the central nervous system (CNS), which inhibits adenosine binding. This inhibits the adenosine-mediated downregulation of CNS activity; thus, stimulating the activity of the medullary, vagal, vasomotor, and respiratory centers in the brain. The anti-inflammatory effects of caffeine are due the nonselective competitive inhibition of phosphodiesterases. Caffeine is used by mouth or rectally in combination with painkillers (such as aspirin and acetaminophen) and a chemical called ergotamine for treating migraineheadaches. It is also used with painkillers for simple headaches and preventing and treating headaches after epidural anesthesia. Caffeine creams are applied to the skin to reduce redness and itching in dermatitis. Healthcare providers sometimes give caffeine intravenously (by IV) for headache after epidural anesthesia, breathing problems in newborns, and to increase urine flow. In foods, caffeine is used as an ingredient in soft drinks, energy drinks, and other beverages.

Caffeine is a methylxanthine alkaloid found in the seeds, nuts, or leaves of a number of plants native to South America and East Asia that is structurally related to adenosine and acts primarily as an adenosine receptor antagonist with psychotropic and anti-inflammatory activities. Upon ingestion, caffeine binds to adenosine receptors in the central nervous system (CNS), which inhibits adenosine binding. This inhibits the adenosine-mediated downregulation of CNS activity; thus, stimulating the activity of the medullary, vagal, vasomotor, and respiratory centers in the brain. The anti-inflammatory effects of caffeine are due the nonselective competitive inhibition of phosphodiesterases. Caffeine is used by mouth or rectally in combination with painkillers (such as aspirin and acetaminophen) and a chemical called ergotamine for treating migraineheadaches. It is also used with painkillers for simple headaches and preventing and treating headaches after epidural anesthesia. Caffeine creams are applied to the skin to reduce redness and itching in dermatitis. Healthcare providers sometimes give caffeine intravenously (by IV) for headache after epidural anesthesia, breathing problems in newborns, and to increase urine flow. In foods, caffeine is used as an ingredient in soft drinks, energy drinks, and other beverages.

Enzastaurin is a serine/threonine kinase inhibitor that showed antiangiogenic, antiproliferative, and proapoptotic properties in vitro and antitumor activity in vivo in a xenograft Waldenström macroglobulinemia (WM) model. Enzastaurin (LY317615) is a potent PKCβ selective inhibitor. Enzastaurin suppresses angiogenesis and was advanced for clinical development based upon this antiangiogenic activity. Enzastaurin suppresses tumor growth through multiple mechanisms: direct suppression of tumor cell proliferation and the induction of tumor cell death coupled to the indirect effect of suppressing tumor-induced angiogenesis. Enzastaurin is an orally administered drug that was intended for the treatment of solid and haematological cancers. Enzastaurin had shown encouraging preclinical results for the prevention of angiogenesis, inhibition of proliferation and induction of apoptosis as well as showing limited cytotoxicity within phase I clinical trials. However, during its assessment in phase II and III clinical trials the efficacy of enzastaurin was poor both in combination with other drugs and as a single agent. Eli Lilly discontinued development of enzastaurin after top-line data from the double-blind, international Phase III PRELUDE trial in 758 DLBCL patients showed that enzastaurin missed the primary endpoint of improving DFS vs. placebo.

Enzastaurin is a serine/threonine kinase inhibitor that showed antiangiogenic, antiproliferative, and proapoptotic properties in vitro and antitumor activity in vivo in a xenograft Waldenström macroglobulinemia (WM) model. Enzastaurin (LY317615) is a potent PKCβ selective inhibitor. Enzastaurin suppresses angiogenesis and was advanced for clinical development based upon this antiangiogenic activity. Enzastaurin suppresses tumor growth through multiple mechanisms: direct suppression of tumor cell proliferation and the induction of tumor cell death coupled to the indirect effect of suppressing tumor-induced angiogenesis. Enzastaurin is an orally administered drug that was intended for the treatment of solid and haematological cancers. Enzastaurin had shown encouraging preclinical results for the prevention of angiogenesis, inhibition of proliferation and induction of apoptosis as well as showing limited cytotoxicity within phase I clinical trials. However, during its assessment in phase II and III clinical trials the efficacy of enzastaurin was poor both in combination with other drugs and as a single agent. Eli Lilly discontinued development of enzastaurin after top-line data from the double-blind, international Phase III PRELUDE trial in 758 DLBCL patients showed that enzastaurin missed the primary endpoint of improving DFS vs. placebo.

Entospletinib (GS-9973) is an adenosine triphosphate competitive inhibitor of Syk that disrupts kinase activity, which is currently in clinical trials for multiple B-cell malignancies. The most common treatment-emergent serious adverse events included dyspnea, pneumonia, febrile neutropenia, dehydration, and pyrexia.

Entospletinib (GS-9973) is an adenosine triphosphate competitive inhibitor of Syk that disrupts kinase activity, which is currently in clinical trials for multiple B-cell malignancies. The most common treatment-emergent serious adverse events included dyspnea, pneumonia, febrile neutropenia, dehydration, and pyrexia.

MK-2206 is an oral selective allosteric inhibitor of Akt that targets all three isoforms of human Akt (Akt-1, Akt-2 and Akt-3). In a phase I study of solid tumors, MK-2206 demonstrated evidence of target modulation and anti-proliferative activity as a single agent and in combination with other agents. Current ongoing trials of MK-2206 include monotherapy and combination therapy in breast cancer, colorectal cancer, haematological malignancies, non-small cell lung cancer and other. Detected treatment-related adverse event are: rash, fatigue, hyperglycemia.