CNS Receptor Ligands

For the latter CNS receptor ligands, different types of chelators have been introduced to the basic receptor binding framework. Originally a bidentate Schiff base was introduced by the reaction of an aliphatic amine with pyridine-aldehyde. Labelling occurred at low concentration and the radio conjugate was physiologically stable. Although receptor affinity was fully retained, brain uptake was low [67]. ACp was introduced at the same position and, as described earlier, and receptor affinity was perfectly retained. No brain uptake data are 

An extension to this work appeared recently when pyridin-2-yl hydrazine based classical chelators were introduced through an ethinyl or ethenyl moiety at position 17. Although still model complexes, this type of derivatization and complexation can easily be transferred to the corresponding 99mTc chemistry. It could be shown that the relative binding affinity was essentially retained and compared favourably with other reported estradiol-derived carbonyl complexes [106]. 

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A comparable challenge is presented by the labeling of CNS receptor ligands, and an excellent review has summarized current development. The potential for the development of " Tc-based... 

The major approaches applied so far for the labeling of CNS receptor ligands are summarized in O Fig. 43.15. 

Scheme4.15 Piano-stool type complexes conjugated to CNS-receptor ligands.

CJ-Receptors are localized ia the brain stem and limbic stmcture, regions associated with endocrine function (76). In the periphery, CJ-receptors are found in the Hver, heart, ileum, vas deferens, and on lymphocytes and thymocytes. Although there is insufficient evidence to clearly define the functional role of CNS CJ-sites, based on the effects of PCP and the interaction of haloperidol with CJ-sites, CJ-receptor ligands may be antipsychotics or used for the treatment of substance abuse. Several CJ-receptor ligands have shown neuroprotective effects in vivo. Ifenprodil (315) and CNS 1102 (316) are being developed for treatment of stroke (Table 18). 

Arylpiperazines have immensely important effects on various and diverse biological targets, in particular on CNS receptors. In the case of serotonin (5-HT) receptors, compounds containing this arylpiperazine moiety represent the largest systematically studied class of 5-HTia receptor ligands [63]. Structural alterations within long-chain arylpiperazines (LCAPs) occur mainly at the two opposite ends of a molecule and have been described by many authors [64-71]. 

Paluchowska MH et al. (1996) Structure-activity relationship studies of CNS agents, part 31 Analogs of MP 3022 with a different number of nitrogen atoms in the heteroaromatic fragment—new 5-HTlA receptor ligands. Arch Pharm (Weinheim) 329(10) 451-456... 

Hayashi, T., Su, T.P. Sigma-1 receptor ligands potential in the treatment of neuropsychiatric disorders. CNS Drugs. 18 269, 2004. 

Substances with a neuromodulatory effect on brain neurotransmitters by direct actions of specific receptors that modify the actions of the transmitters listed include prostaglandins, adenosine, enkephalins, substance P, cholecystokinin, endorphins, endogenous benzodiazepine receptor ligands, and possibly histamine. CNS, central nervous system. NMDA, N-methyl-D-aspartate. Strych, strychnine. 

Muscarinic M3 Exocrine glands, vessels (smooth muscle and endothelium) CNS neurons Like M receptor-ligand binding... 

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