Although pirenzepine is classed as an M
1-selective muscarinic antagonist, the chick model does not possess an M
1-receptor (Yin GC, et al.
IOVS 2003;44:ARVO E-Abstract 4339), which raises questions about the specific receptor-based mechanism by which pirenzepine mediates ocular growth. However, the binding affinity of pirenzepine to the mammalian M
4-receptor is only four times lower than for the mammalian M
1-receptor, and the affinity of pirenzepine for the chick M
2-receptor (M
1 surrogate in the chick) is nearly the same as its affinity for the M
4-receptor.
25 Thus, pirenzepine may mediate its effects through the M
4 or M
2 receptor (Yin GC, et al.
IOVS 2003;44:ARVO E-Abstract 4339).
25 More recently, the highly selective M
4 antagonist MT3 has been shown to be effective in reducing experimentally induced myopia and axial elongation in chicks (Morgan IG, et al.
IOVS 2005;46:ARVO E-Abstract 3342; Diether S, et al.
IOVS 2005;46:ARVO E-Abstract 1986; McBrien NA, et al.
IOVS 2009;50:ARVO E-Abstract 3850). Although the M
4-receptor pathway seems most likely, recently it has been reported (Diether S, et al.
IOVS 2005;46:ARVO E-Abstract 1986; McBrien NA, et al.
IOVS 2009;50:ARVO E-Abstract 3850) that the highly selective M
1 muscarinic antagonist MT7 is partially effective in reducing experimental myopia in the chick model of refractive development. This finding could be interpreted to indicate that multiple muscarinic receptors are involved in the regulation of ocular growth and myopia, although the highly selective nature of MT3 and -7 have yet to be confirmed with binding assays; thus, nonspecific effects cannot be ruled out.