On the mechanism of action of 2-amino-4-methylpyridine, a morphine-like analgesic.

2-Amino-4-methylpyridine (2-AMP), when implanted into the ventral lateral thalamus of rats, does not cause stereotyped behavior. On the other hand, when compulsive biting and gnawing was evoked by thalamic implants of morphine (via stimulation of type 1 opiate receptors, which activate a dopaminergic mechanism) or of apomorphine, systemic application of 2-AMP suppressed this response. The anti-gnawing effect of 2-AMP was abolished by naloxone, indicating that the inhibitory action of 2-AMP involves activation of another, viz. type 2 receptor. The antagonistic influence of 2-AMP could also be suppressed by pretreatment of the rats with p-chlorophenylalanine. It is concluded that 2-AMP has only a weak effect on type 1 opiate receptors, linked to a dopaminergic mechanism, but it possesses high affinity to type 2 opiate receptors, which are connected with serotonergic pathways.