What is the mechanism behind respiratory depression with the use of imipramine and amitriptylline (the TCAs) at toxic levels. Im assuming that it has to do with muscarinic receptor blockade?
The TCAs inhibit neuronal uptake which is their main mechanism of action. Most of the agents have some muscarinic and alpha-blocking activity. At high toxic doses these actions become prominent ie. Antimuscarinic effects: tachycardia, constipation, urinary retention, blurred vision, dry mouth; Alpha-blocking effects: hypotension, postural hypotension. At higher doses such as seen during suicides, coma and respiratory depression occur through blockade of CNS muscarinic receptors.
