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Pharmacological actions of potassium-channel openers
iences, University of Manchester, Oxford Road U.K.
xtures. the
bio
plied to a diverse group of smooth muscle relaxants, all of which smooth muscle. Seven distinct types of KC0 have already been g type substances are:- 1) benzopyran, cromakalim 2) cyanoguani4) tbioformamide_ RP 49356 5) pyrimidine oxide sulphate, minoxidil 6) dine, niguldipine. Cromakalim, pinacidil, RF 49356 and niguldipine are y active components of which are BRL 38227, (- )-pinacidil, RP 52891 and
pressure with reflex tachycardia. Effects on flow to specific vascular . There may be selective vasodilator effects on blood vessels in n other smooth muscle-containing structures such as uterus and detected. In vitra KCOs inhibit spontaneous electrical arid mechanical discharges in all types muscle, effects which are usually accompanied by a marked hyperpolarisation which is well maintained. Ion ave shown that KCOs increase the rate of both 42K and “Rb exchange in tissues me preliminary evidence of selective effects on “K efflux with little effect on =Rb tro effects of KCOs can be antagonised by oral hypoglycaemic benclamide. suggesting that a K-channel with properties similar to that of the ATP-dependent c muscle may be involved. variously suggested that BK,,, K, or K, channels represent the site of action of the KCOs; the antagonistic effects of glibenclamide favour the involvement of K,, although the ghbenclamide for K,, in smooth muscle in questionable. ty of KCOs to antagonise contractions produced by agonist-induced Ca release from intracellular stores t the actions of KCOs at plasmaiemmal K-channels may be insufficient to account totally for their smooth muscle relaxant effects. a decrease in bl
1* S.we.19.3
dicvn Cbicol
Research Ltd. Svanemellev~
2. UK-2100 Copenhagen 0, Denmark
Currently at least four agents are considered as K channel openers: Cromakalim, EMD 52 692, Nicorandil and Pinacidil. Pinacidii has been registered in several countries and was recently approved by the US FDA for the treatment of arterial hypertension. Nicorandil has been marketed for the treatment of angina pectoris, but only in Japan. The other drugs are under development. is the K channel opener that has been most thoroughly evaluated. For the treatment of arterial it has been compared to placebo, methyldopa, prazosin, hydralazine Lnd nifedipine in monotherapy or in comb~~a~o~ with a thiazide diuretic. The response rate for Pinacidil treated patients with mild to moderate h~e~ens~o~ was higher than placebo, prazosin and hydralazine and the same as-for methyldopa and nifedipine. The main adverse reactions are those of a vasodilating agent, i.e. oedema, vascular headache and palpitations. When
xtures. the
bio
plied to a diverse group of smooth muscle relaxants, all of which smooth muscle. Seven distinct types of KC0 have already been g type substances are:- 1) benzopyran, cromakalim 2) cyanoguani4) tbioformamide_ RP 49356 5) pyrimidine oxide sulphate, minoxidil 6) dine, niguldipine. Cromakalim, pinacidil, RF 49356 and niguldipine are y active components of which are BRL 38227, (- )-pinacidil, RP 52891 and
pressure with reflex tachycardia. Effects on flow to specific vascular . There may be selective vasodilator effects on blood vessels in n other smooth muscle-containing structures such as uterus and detected. In vitra KCOs inhibit spontaneous electrical arid mechanical discharges in all types muscle, effects which are usually accompanied by a marked hyperpolarisation which is well maintained. Ion ave shown that KCOs increase the rate of both 42K and “Rb exchange in tissues me preliminary evidence of selective effects on “K efflux with little effect on =Rb tro effects of KCOs can be antagonised by oral hypoglycaemic benclamide. suggesting that a K-channel with properties similar to that of the ATP-dependent c muscle may be involved. variously suggested that BK,,, K, or K, channels represent the site of action of the KCOs; the antagonistic effects of glibenclamide favour the involvement of K,, although the ghbenclamide for K,, in smooth muscle in questionable. ty of KCOs to antagonise contractions produced by agonist-induced Ca release from intracellular stores t the actions of KCOs at plasmaiemmal K-channels may be insufficient to account totally for their smooth muscle relaxant effects. a decrease in bl
1* S.we.19.3
dicvn Cbicol
Research Ltd. Svanemellev~
2. UK-2100 Copenhagen 0, Denmark
Currently at least four agents are considered as K channel openers: Cromakalim, EMD 52 692, Nicorandil and Pinacidil. Pinacidii has been registered in several countries and was recently approved by the US FDA for the treatment of arterial hypertension. Nicorandil has been marketed for the treatment of angina pectoris, but only in Japan. The other drugs are under development. is the K channel opener that has been most thoroughly evaluated. For the treatment of arterial it has been compared to placebo, methyldopa, prazosin, hydralazine Lnd nifedipine in monotherapy or in comb~~a~o~ with a thiazide diuretic. The response rate for Pinacidil treated patients with mild to moderate h~e~ens~o~ was higher than placebo, prazosin and hydralazine and the same as-for methyldopa and nifedipine. The main adverse reactions are those of a vasodilating agent, i.e. oedema, vascular headache and palpitations. When