Therapeutic use:Reserpine is effective but has significant adverse effects.It is a 3rd line AHD.The drug is inexpensive,and the effect stays long even after the drug disappears from circulation.Effective when used at low dose(0.05 mg),in combination with diuretics. Adverse effect and toxicity:Enters brain easily and can produce sedation, mental depression,Parkinson's like symptom.Reserpine should not be given to patients with mental depression or peptic ulcer(for stimulating gastric acid secretion). Guanethidine瓢乙啶and guanadrel Mechanism of action:(1)Inhibition of NE release from sympathetic nerve ending. (2)gradual depletion of NE stores in the nerve ending.Guanethidine enters cell through uptake 1,which also recaptures NE.Cocaine and tricyclic antidepressant block uptake 1 and reduce the effect of quanethidine. NH Tyrosine N- Deplete NE Guanethidine Transport blocked by cocaine.TCA AT presynaptic Jpt ATP G G NE Ca G=guanethidine 「Block NE NE=norepinephrine release 1414 Therapeutic use: Reserpine is effective but has significant adverse effects. It is a 3rd line AHD. The drug is inexpensive, and the effect stays long even after the drug disappears from circulation. Effective when used at low dose (0.05 mg), in combination with diuretics. Adverse effect and toxicity: Enters brain easily and can produce sedation, mental depression, Parkinson’s like symptom. Reserpine should not be given to patients with mental depression or peptic ulcer (for stimulating gastric acid secretion). Guanethidine 胍乙啶 and guanadrel Ca2+ Na+ Tyrosine Tyrosine Dopa TH DD Dopamine (DA) NE DBH ATP Ca2+ NE ATP α2R NE (-) G G G G Uptake 1 G G presynaptic Block NE release Deplete NE in vesicle Transport blocked by cocaine, TCA G G G G NE G = guanethidine NE = norepinephrine Mechanism of action: (1) Inhibition of NE release from sympathetic nerve ending. (2) gradual depletion of NE stores in the nerve ending. Guanethidine enters cell through uptake 1, which also recaptures NE. Cocaine and tricyclic antidepressant block uptake 1 and reduce the effect of guanethidine