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1. Under certain conditions D-lysergic acid diethylamide (LSD), 10^-9-10^-6 g/ml., exerted an immediate, prolonged and slowly reversible inhibitory effect upon the post-ganglionic motor transmission in desheathed guinea-pig vas deferens preparations.

2. The most critical factor influencing this action of LSD appeared to be the train length. With short trains of less than 4 or 5 pulses the twitch inhibition produced by LSD was often total. With longer trains (5-20 pulses), the degree of inhibition declined with increase in train length. These results suggest the existence of two components in the motor response to post-ganglionic stimulation, distinguished by their susceptibility to LSD.

3. The inhibition of the LSD-susceptible component was related to the dose of LSD in the range 10^-9-10^-6 g/ml., reaching a maximum at 0·5-1 x 10^-6 g/ml. The response remnants elicited by trains of more than 5 pulses under these conditions could not be reduced further by a ten- to twenty-fold increase in LSD concentration to 10^-5 g/ml. and were in fact slightly potentiated.

4. The inhibition of post-ganglionic motor transmission by LSD was not explicable on the basis of an -adrenoceptor blockade because it was not associated with any reduction in motor responses to noradrenaline.

5. The use of propranolol excluded mediation of the LSD-inhibition by -adrenoceptors.

6. The LSD effect was not due to a non-specific smooth muscle depression because it was not associated with any reduction in motor responses to acetylcholine, ATP or bradykinin.

7. The inhibitory effect of LSD on post-ganglionic transmission resembled that of noradrenaline in that it was antagonized by phentolamine; another -adrenoceptor blocking agent, phenoxybenzamine, was less effective than phentolamine in this respect.

8. The LSD-inhibition was obtained in preparations taken from reserpinized guinea-pigs.

9. The inhibition of motor transmission in the vas deferens by LSD was confirmed in rats, Meriones shawii and rabbits.

10. The inhibition of post-ganglionic transmission by LSD was unrelated to its ability to antagonize 5-hydroxytryptamine (5-HT), to which the longitudinal muscle of the guinea-pig vas deferens is insensitive. The more potent 5-HT antagonists, methysergide and BOL 148 were either virtually inactive or considerably weaker than LSD.