Contraction Of Rat Anococcygeus Muscle Research Articles

Synthesis and Pharmacological Evaluation of New 1-Hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines as Norepinephrine Potentiators

4-Hydroxy-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline (PI-OH) (1a) and its derivatives form a new class of compounds which possess norepinephrine (NE) potentiating activity. As a new series of compounds, 1-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines (2a--f) were synthesized by the intramolecular Barbier reaction of N-[2-(2-iodophenyl)ethyl]phenacylamines (6a--f) with n-BuLi as a key reaction step. The potentiating activities of the benzazepines 2a--f on the contraction of rat anococcygeus muscle induced by NE were tested. Among the compounds tested in this study, compound 2a showed moderate potentiating activity (the activity ratio was 7.3-fold at 3 x 10(-5) M).

Differential effects of nifedipine on nerve-mediated and noradrenaline-evoked contractions of rat anococcygeus muscle

In rat anococcygeus muscle the inhibitory effect of nifedipine (0.01, 0.1, 1.0 and 10 μM) was determined on adrenergic twitches in response to electrical field stimulation (trains of 4 pulses, 0.1 ms pulse duration, 10 Hz) and on twitch-matching contractions evoked by noradrenaline. Nifedipine concentration-dependently reduced the neurogenic twitch with an IC 50 of 0.083 μM. Nifedipine reduced the noradrenaline-evoked contraction to a markedly lesser degree (IC 50 > 10 μM). The difference in the magnitude of inhibition of electrically evoked twitch and twitch-matching noradrenaline-evoked contraction was statistically significant at every concentration of nifedipine. It is concluded that inhibition of the twitch by nifedipine involves some other mechanism(s) in addition to its Ca 2+ channel blocking property in smooth muscle.

Lack of effect of D600 on α1-adrenoceptor-mediated contractions of rat isolated anococcygeus muscle

The experiments concerned the contractile responses of rat anococcygeus muscle to the selective α 1-adrenoceptor agonists cirazoline, phenylephrine, methoxamine, St 587, Sgd 101/75, amidepphrine and SK&F 89748-A and the effect of the calcium entry blocker D600 on the responses. The effects of noradrenaline, adrenaline, K +, tyramine and electrical field stimulation were studied as well. The potency series of the various agonists on rat anococcygeus muscle differed from the series for rat and guinea-pig aorta, indicating differences in the structure of the α 1-adrenoceptors on these tissues. D600 was ineffective in inhibiting contractions of rat anococcygeus muscle to the various agonists, but effectively attenuated the responses to K + in anococcygeus muscle from rats pretreated with reserpine or in prazosin-induced preparations. These data indicate that α 1-adrenoceptor activation in rat anococcygeus muscle triggers contractions which do not primarily require the influx of extracellular calcium. In this respect, the smooth muscle from the rat anococcygeus muscle differs from vascular smooth muscle from this species.