Figure 6.

Proposed effects of amiloride derivation on the hGABA-(A)ρ1 receptor. When the guanidine group is accessible and the pyrazine ring remains unchanged, as in the case of amiloride, there is positive allosteric modulatory activity and weak direct activity on the hGABA-A ρ1 receptor. The HMA structure is produced from derivation of the pyrazine ring along with accessibility of the guanidine group. If there is a substitution on the guanidine group, however, the resulting derivative fails to elicit positive allosteric modulatory activity from the receptor, as in the case of benzamil and phenamil.