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Drugs online research references

Teratology. 1984 Aug;30(1):39-45.
Incidence and potentiation of external and internal fetal anomalies resulting from chlordiazepoxide and amitriptyline alone and in combination.

Beyer BK, Guram MS, Geber WF.

The teratogenic potential of a combination of chlordiazepoxide (Cdz) and amitriptyline (Amt) was examined with regard to both internal and external anomalies. Timed pregnant golden hamsters were given a single intraperitoneal injection on day 8 of gestation of one of the following: chlordiazepoxide hydrochloride (28.5 mg/kg), amitriptyline hydrochloride (70.3 mg/kg), Cdz-Amt combination (28.5 mg/kg Cdz + 70.3 mg/kg Amt, in order to retain the 1:2.5 dose ratio utilized in a clinically-used preparation of these agents), or saline vehicle (control). Fetuses were recovered on gestation day 15 following maternal sacrifice. Cranial malformations were analyzed in Bouin's-fixed fetuses by making 1-mm coronal sections through each head, whereas visceral anomalies were examined following general dissection of each body. Amt alone produced a significant (P less than 0.05) incidence of bent tail and encephalocele, whereas Cdz significantly (P less than 0.05) altered the male:female ratio of surviving fetuses when compared with saline-injected controls. The Cdz-Amt combination caused significant increases in cranial malformations, open eye, bent tail, abnormal lung, and urogenital anomalies. The teratogenic effects of potentiation between the components of this combination are discussed in terms of external and internal malformations.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6435276&dopt=Abstract

Arch Androl. 1984;12(1):25-8.
Sperm immobilizing potency of amitriptyline and imipramine: measured with transmembrane migration.

Hong CY, Chiang BN, Ku J.

The inhibitory effect of amitriptyline and imipramine on human sperm motility was measured in vitro with a transmembrane migration method. The EC50 for amitriptyline and imipramine were 170 microM and 160 microM respectively. They were more potent than any other drug that had been tested on this pharmacological model. Transmembrane migration method was less sensitive than turbidimetric method to detect the sperm immobilizing effect of drugs.

PIP: The sperm immobilizing effect of 2 frequently prescribed antidepressants--amitriptyline and imipramine--was measured with a transmembrane migration method. Results were compared with those obtained by torbidimetric method. In addition, the potencies of these 2 drugs were compared with other sperm immobilizing agents, so the underlying mechanism and clinical implication could be elucidated. Fresh human semen samples were collected from healthy donors. Drug treated sperm motility was calculated from the proportion of sperm that moved across the membrance from semen drug mixture into phosphate buffered saline during 2 hour incubation at 37 degrees Centigrade. The motility of sperm in semen mexed with phosphate buffered saline was used as control. The drug treated sperm motility was expressed as percentage of control and plotted on a semilog paper. The concentration of drug that decreased sperm motility of 50% of control (EC50) was obtained from the concentration response curve. The EC50 for amitriptyline and imipramine were 170 mcgM and 160 mcgM, respectively. The difference between these 2 drugs at all concentrations was not significant. The clinical implication for determing the sperm immobilizing potency of drugs in vitro is uncertain at this time. The EC50 is nearly a hundred times higher than the therapeutic blood levels of these drugs. In addition, such an in vitro test investigates the acute effect of drugs only; longterm effect, as well as the effect of the metabolites, were not included. The potential value of developing sperm motility as a cellular model for pharmacological research is confirmed in this study.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6476965&dopt=Abstract

Neurotoxicology. 1982 Nov;3(3):83-90.
Comparative teratogenicity of chlordiazepoxide, amitriptyline, and a combination of the two compounds in the fetal hamster.

Guram MS, Gill TS, Geber WF.

A combination of chlordiazepoxide and amitriptyline maternally administered as a single intraperitoneal injection on day 8 of gestation in the fetal hamster produced predominantly central nervous system anomalies including exencephaly and encephalocoele. In addition, omphalocoele, spinal flexion, and microcephaly were noted. A dose response relationship was found in which a maternal dose range of 13/33 mg/kg--33/83 mg/kg chlordiazepoxide/amitriptyline produced 7-92 percent fetal anomalies. Combination drug dose levels up to 23/58 mg/kg produced no maternal mortality. However, higher levels did result in a marked dose dependent mortality rate. The teratogenic potential of the combined drugs is much more pronounced than that of either drug administered alone since chlordiazepoxide at a maternal dose range of 280/3100 mg/kg produced 3-55 percent fetal anomalies, and amitriptyline at a maternal dose range of 60-100 mg/kg produced 6-45 percent fetal anomalies. The majority of these aberrant fetal developmental entities also were classifiable as exencephaly and encephalocoeles. Dose-dependent maternal mortality was observed at all dose levels for each drug administered separately.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6891762&dopt=Abstract

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