Calcium antagonists/modulators

Hollt, V., M. Kouba, M. Dietel, and G. Vogt. 1992. Stereoisomers of calcium antagonists which differ markedly in their potencies as calcium blockers are equally effective in modulating drug transport by P-glycoprotein. Biochem Pharmacol 43 2601. 

Iqbal N, Akula MR, Vo D et al (1998) Synthesis, rotamer orientation, and calcium channel modulation activities of alkyl and 2-phenethyl 1, 4-dihydro-2, 6-dlmethyl-3-nltro-4-(3- or 6-substltuted-2-pyrldyl)-5-pyridinecarboxylates. J Med Chem 41 1827-1837 LI RWS, Tse CM, Man RYK et al (2007) Inhibition of human equilibrative nucleoside transporters by dihydropyridine-type calcium channel antagonists. Eur J Pharmacol 568 75-82 Cosconatl S, Marlnelli L, Lavecchia A et al (2007) Characterizing the 1,4-dlhydropyrldlnes... 

Calcineurin and Downstream regulatory element antagonist modulator (DREAM) are two proteins that are involved in calcium-regulated transcription control pathways. There are several such pathways. One is through calmodulin-dependent kinase, such as CaM kinase 1, CaM-kinase IV, or CaM kinase kinase. The other is through SIOOB that interacts with the tumor suppressor p53 to regulate its transcriptional activity. Both the CaM kinases and SIOOB have been discussed earlier. Here we will focus on calcineurin and DREAM. 

Subramanian VB, Bowles MJ, Khnrmi NS, Davies AB, O Hara MJ, Raftery EB. Calcium antagonist withdrawal syndrome objective demonstration with frequency-modulated ambulatory ST-segment monitoring. BMJ (Clin Res Ed) 1983 286(6364) 520-1. 

Slow Calcium Channel Blockers (SCCBs), which are also referred to as calcium entry blockers and even, erroneously, as calcium antagonists, are a number of marketed drugs, several of which have no chemical relationship to the others. They will be discussed in some detail with the anti-anginal drugs (see later). At this point, suffice it to state that their antihypertensive effect is due to their ability to modulate the influx of Ca2+ across the cell membrane of the arterial smooth muscle. This will reduce Ca2+-promoted activation of the cells contractile proteins, leading to vasodilation. 

Shan R, Velazquez C, Knaus EE (2004) Syntheses, calcium channel agonist-antagonist modulation activities, and nitric oxide release studies of nitrooxyalkyl l,4-dihydro-2,6-dimethyl-3-nitro-4-(2,l,3-benzoxadiazol-4-yl)pyridine-5-carboxylate racemates, enantiomers, and diastereomers. J Med Chem 47 254-261... 

Calcium channels have been shown to play a role in epilepsy as well [23]. Currently used antiepileptic drugs exhibit a wide spectrum of activity, including modulation of voltage-gated sodium and calcium channels. T-type calcium channels have been demonstrated to play an important role in absence epilepsy, a specific form of epilepsy characterized by brief lapses in consciousness correlated with spike-and-wave discharges in the electroencephalogram [14,24-28]. Ethosuximide 1 has been shown to block T-type calcium channels and is used clinically to treat absence epilepsy [25]. Several selective small-molecule T-type calcium channel antagonists have demonstrated efficacy in rodent epilepsy models (vide infra). 

Several different types of serotonin receptor (for example, S-HTi / 5-HT2A/ 5-HT2C/ 5-HTib/id) have been associated with the motor side effects of the SSRIs which may arise should these drugs be administered in conjunction with a monoamine oxidase inhibitor. The 5-HT3 receptor is an example of a non-selective cation charmel receptor which is permeable to both sodium and potassium ions and, because both calcium and magnesium ions can modulate its activity, the 5-HT3 receptor resembles the glutamate-NMDA receptor. Antagonists of the 5-HT3 receptor, such as ondansetron, are effective antiemetics and are particularly useful when... 

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