Isorhynchophylline is a plant alkaloid isolated from Uncaria species with therapeutic potential for cardiovascular and central nervous system diseases. The antihypertensive effect of isorhynchophylline was firstly observed in 1989, which was strongly linked to the traditional use of Uncaria species (Gouteng in Chinese). Isorhynchophylline and rhynchophylline were the main hypotensive constituents in Uncaria rhynchophylla. In rat isolated mesenteric arteries and tail artery, isorhynchophylline inhibited the increased infusion pressure induced by high K+ and norepinephrine in a concentration-dependent manner. The potency of isorhynchophylline and rhynchophylline was similar in mesenteric arteries, but in the tail artery, the effect of isorhynchophylline on high K+ induced infusion pressure increase was stronger than that of rhynchophylline, and there was a similar trend in the contractile response induced by norepinephrine. Isorhynchophylline also inhibited the hypertensive effect of angiotensin II. The results indicate that in small blood vessels of rat, isorhynchophylline can directly inhibit the contractile responses induced by several agonists. In vivo, ouabain and CaCl2 were used to establish experimental arrhythmic models in guinea pigs and rats. In vitro, the whole-cell patch-clamp technique was used to study the effect of isorhynchophylline on action potential duration and calcium channels in acutely isolated guinea pig and rat cardiomyocytes. Isorhynchophylline, infusion 0–16 mg/kg at a constant rate, dose-dependently decreased heart rate, prolonged sinus node recovery time, and PR, AH, HV intervals. Isorhynchophylline significantly inhibited the heart rate and atrioventricular conduction. These inhibitory effects of isorhynchophylline were partially antagonized by isoprenaline, but not by atropine. Isorhynchophylline inhibited the automaticity and contractile force of isolated guinea pig atrium in a concentration-dependent manner. Isorhynchophylline significantly depressed adrenaline-induced automaticity, and prolonged functional refractory period and decreased excitability. Furthermore, 10 μmol/L of isorhynchophylline reduced the effect of ouabain on the contractile force in the left atrium and significantly inhibited the response to paired stimulation. In anesthetized dogs, isorhynchophylline markedly reduced the tension-time index which indicated myocardial oxygen consumption. The result indicates that the decrease of myocardial oxygen consumption by isorhynchophylline would protect the heart against ischemia induced by hypertension. Isorhynchophylline showed a mild central depressive effect in mice. Isorhynchophylline significantly decreased locomotor activity after oral administration to mice. The depression of locomotor activity upon administration of the alkaloid appears to be due to mediating of the central dopaminergic system. Isorhynchophylline dose-dependently inhibited 5-hydroxytryptamine (5-HT)2A receptor-mediated head-twitch but not 5-HT1A receptor-mediated head-weaving responses evoked by 5-methoxy-N, N-dimethyltryptamine. Isorhynchophylline attenuated the in vitro ischemia-induced neuronal damage in a dose-dependent manner. Isorhynchophylline protects against glutamate-induced neuronal death in cultured cerebellar granule cells by inhibition of Ca2+ influx. Pretreatment with isorhynchophylline significantly elevated cell viability, decreased the levels of intracellular reactive oxygen species and malondialdehyde, increased the level of glutathione, and stabilized mitochondrial membrane potential in β- amyloid(25–35)-induced neurotoxicity in rat pheochromocytoma cells. In unthoracotomized dogs, isorhynchophylline (5 mg/kg, iv) reduced the mean arterial pressure but did not affect renal blood flow. Isorhynchophylline did not block nictitating membrane contraction induced by stimulating collum sympathetic nerve and did not decrease blood pressure after injected in the cerebral ventricle.