C. A. Stone, M. Torchiana, A. Navarro
Jun 1, 1956
Citations
3
Influential Citations
107
Citations
Quality indicators
Journal
The Journal of pharmacology and experimental therapeutics
Abstract
Certain pharmacologic properties of 3-methylaminoisocamphane (mecamylamine) have been reported. These studies indicate that this secondary amine possesses ganglionic blocking properties characterized by a high order of potency, specificity and a long duration of action. The ganglionic blocking nature of the compound was revealed by its ability to inhibit the contractions of the nictitating membrane in cats induced by preganglionic nerve stimulation, but not those due to injected epinephrine. Likewise, the ganglionic blocking activity was probably responsible for the blocking effect observed on nicotine vascular and respiratory responses in cats and dogs, as well as on the vascular responses to carotid occlusion and peripheral vagal stimulation. The prolonged vasodepressor effect and change in heart rate that followed its administration were most likely due to ganglionic blockade, although an additional central nervous system site of action has not been excluded. In comparison with two conventional quaternary ammonium ganglionic blocking agents (hexamethonium and pentolinium), no important qualitative differences have been revealed. Quantitatively, mecamylamine was found to be equipotent with hexamethonium and one-fourth as active as pentolinium in inhibiting preganglionically-induced contractions of the nictitating membrane of cats. On the other hand, mecamylamine and pentolinium were about equiactive with respect to inhibition of nicotine pressor responses and both were two to four times more active than hexamethonium in this respect. The duration of action of the non-quaternary ammonium blocking agent exceeded that of these quaternary ammonium derivatives by three to five or more times in all experiments in which direct comparisons were made. The relatively low ratio between the oral and intravenous LD509s, as determined in mice, indicated that mecamylamine was considerably better absorbed following oral administration. In this respect, the ratios for tetraethylammonium, pentolinium, hexamethonium and chlorisondamine were four to six times larger than the corresponding ratio for mecamylamine. Mecamylamine did not possess demonstrable adrenergic blocking, antihistaminic, atropine-like or surface local anesthetic properties. In common with hexamethonium and pentolinium, the non-quaternary ammonium agent was found to potentiate the vascular effects of pressor and depressor substances in the dog and to produce measurable, but weak, curare-like effects. This latter property of mecamylamine was insignificant as compared to its ganglionic blocking activity. These findings were interpreted to indicate a reasonably high degree of specificity and selectivity of ganglionic blocking action.