Antagonism to Dopaminergic Stereotypy, and Convulsant and Hypertensive Effects by 2-Amino-4-Methylpyridine

Publisher Summary This chapter discusses antagonism to dopaminergic stereotypy and convulsant and hypertensive effects by 2-amino-4-methylpyridine (2-AMP). 2-AMP resembles morphine in some pharmacological properties but differs from the opiate in others. Thus, the implantation of morphine into the lateral thalamus of rats causes stereotyped behavior, but the deposition of 2-AMP into this region is ineffective. The thalamic application of apomorphine also evokes stereotypy. Thus, this effect is because of direct or indirect activation of dopamine receptors; on this mechanism, 2-AMP has no influence. On the other hand, systemic morphine suppresses stereotyped behavior, caused by injection of apomorphine or by thalamic implantation of morphine, and a similar inhibition is produced by systemic 2-AMP. The antagonistic effect of either morphine or 2-AMP against stereotypy is abolished by the pretreatment of the rats with p -chlorophenylalanine and may, therefore, be ascribed to the activation of an inhibitory serotonergic mechanism. Large i.v. doses of 2-AMP produce convulsions in wake rabbits but are rather ineffective in cats under pentobarbitone anesthesia or in spinal or pithed cats. Whenever seizures appear, they are accompanied by a sharp and prolonged rise of blood pressure in marked contrast to the morphine-induced hypotension.