Effects of McN-6186 on voltage-dependent Ca++ channels in heart and pituitary cells

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 248; no. 1; pp. 164 - 170
• Main Authors: RAMPE, D, SKATTEBØL, A, TRIGGLE, D. J, BROWN, A. M
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.01.1989
• Subjects: Amphetamines - pharmacology; Animals; Barium - metabolism; Biological and medical sciences; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium Channels - drug effects; Cardiovascular system; DOM 2,5-Dimethoxy-4-Methylamphetamine - analogs & derivatives; DOM 2,5-Dimethoxy-4-Methylamphetamine - pharmacology; Heart - drug effects; Isradipine; Medical sciences; Membrane Potentials - drug effects; Miscellaneous; Oxadiazoles - metabolism; Pharmacology. Drug treatments; Pituitary Gland - drug effects; Rats; Tumor Cells, Cultured; Heart; Cell culture; Brain; Calcium; Newborn animal; Calcium antagonist; Electrophysiology; Ionic current; In vitro; Biological activity; Tumor cell; Myocyte
• ISSN: 0022-3565; 1521-0103

McN-6186 (N-[2-(3,5-dimethoxyphenyl)ethyl]-5-methoxy-alpha-methyl-2 -(phenylethynyl) benzeneethanamine hydrochloride is a compound structurally distinct from other Ca++ channel ligands. McN-6186 showed some stimulation of 1,4-dihydropyridine-sensitive Ca++ uptake in neonatal rat ventricular cells at concentrations of 1 and 3 nM. At higher concentrations McN-6186 inhibited this uptake in rat ventricular cells at concentrations approximately 100-fold less than those needed to block the corresponding Ca++ uptake in rat anterior pituitary (GH3) cells. McN-6186 (2 microM) inhibited L-type Ca++ channel current in neonatal rat ventricular cells in a voltage-dependent manner while having little or no effect on this current in GH3 cells. In some ventricular cells tested, the T-type Ca++ current was also blocked by 2 microM McN-6186. McN-6186 inhibited (+)-[3H]PN200-110 binding in rat cardiac membranes with an IC50 value of 1.45 X 10(-7) M and a shallow Hill slope (nH = 0.42). It is concluded that McN-6186 blocks L-type Ca++ channels in heart cells preferentially to those found in GH3 cells. Furthermore, McN-6186 may have other sites and mechanisms of action in addition to L-type Ca++ channel blockade.