1. Diphenoxylate
No data exist on the use of diphenoxylate during breastfeeding. One expert panel considers diphenoxylate to be unacceptable during breastfeeding.[1] Based on its chemical and pharmacological similarity to narcotics, occasional small doses of diphenoxylate may be acceptable while breastfeeding an older infant, but alternatives are preferred, especially while nursing a newborn.
2. GABA-mimetic activity and effects on diazepam binding of aminosulphonic acids structurally related to piperidine-4-sulphonic acid
P Krogsgaard-Larsen, P Jacobsen, E Falch, D R Curtis J Neurochem . 1985 Jan;44(1):68-75. doi: 10.1111/j.1471-4159.1985.tb07114.x.
The relationship between structure, in vivo activity, and in vitro activity of some analogues of the gamma-aminobutyric acid (GABA) agonist piperidine-4-sulphonic acid (P4S) was studied. The syntheses of 1,2,3,6-tetrahydropyridine-4-sulphonic acid (DH-P4S) and (RS)-pyrrolidin-3-yl-methanesulphonamide (PMSA-amide) are described. Like P4S, its unsaturated analogue DH-P4S and the five-ring isomer (RS)-pyrrolidin-3-yl-methanesulphonic acid (PMSA) were bicuculline methochloride (BMC)-sensitive inhibitors of the firing of neurones in the cat spinal cord. Whereas isonipecotic acid was less potent than its unsaturated analogue isoguvacine as a GABA-mimetic and as an inhibitor of GABA binding, the opposite relative potencies of P4S and DH-P4S were observed, P4S being proportionally more potent than DH-P4S. In contrast with P4S and DH-P4S, PMSA, which is an analogue of the potent GABA uptake inhibitor and BMC-sensitive GABA-mimetic homo-beta-proline, was a relatively weak inhibitor of GABA uptake in vitro. PMSA-amide was more than two orders of magnitude weaker than PMSA as an inhibitor of GABA binding and did not significantly affect GABA uptake in vitro. The effects of 3-aminopropanesulphonic acid (3-APS), PMSA, P4S, and DH-P4S on the binding of [3H]diazepam in vitro at 30 degrees C, in the presence or absence of chloride ions, were studied and compared with those of the structurally related amino acids GABA, homo-beta-proline, isonipecotic acid, and isoguvacine. Under these conditions the aminosulphonic acids were weaker than the respective amino acids in enhancing [3H]diazepam binding, the difference being more pronounced in the absence of chloride.
3. Esters of nipecotic and isonipecotic acids as potential anticonvulsants
C N Hinko, T T Tita, A M Crider, J D Wood J Pharm Sci . 1982 Nov;71(11):1214-9. doi: 10.1002/jps.2600711108.
A variety of esters of nipecotic and isonipecotic acids were synthesized and evaluated for anticonvulsant activity. The ester group was varied in terms of lipophilicity and reactivity toward hydrolysis. The esters were screened against seizures induced by electroshock, pentylenetetrazol, and the putative gamma-aminobutyric acid antagonist, bicuculline. The most significant activity was demonstrated by the p-nitrophenyl esters of nipecotic and isonipecotic acids against bicuculline-induced seizures. Esters of nipecotic acid were tested for in vitro inhibition of gamma-aminobutyric acid and L-proline uptakes into mouse whole brain minislices. The p-nitrophenyl, n-octyl, and succinimidyl esters were the most potent inhibitors of gamma-aminobutyric acid uptake. The uptake of gamma-aminobutyric acid by the ester derivatives appeared to involve specific and nonspecific mechanisms.
