Luteolytic hormones are calcium-mediated, guanine nucleotide antagonists of gonadotropin-sensitive adenylate cyclase.

We suggest that regression of the corpus luteum is an active process induced by PGF2 alpha, GnRH, and a peptide of ovarian origin whose action GnRH mimics (20). The initial events involved in luteolysis occur within minutes, and they are intimately linked to inhibition of LH action. Membrane receptor binding of luteolytic hormones activates production of a second messenger (such as a product of PI turnover) that stimulates release of sequestered, intracellular Ca2+ by a mechanism linked to inhibition of microsomal Ca2+-ATPase activity. The increase in cytosolic Ca2+ inhibits adenylate cyclase activity by blocking GTP-dependent activation of adenylate cyclase. As a result, the cell response to LH is abolished and function is lost.

Methsuximide for complex partial seizures: efficacy, toxicity, clinical pharmacology, and drug interactions.

Methsuximide (MSM; Celontin) was administered for 8 weeks to 26 patients with complex partial seizures (CPS) refractory to phenytoin and carbamazepine and phenobarbital or primidone. A 50% or greater reduction in CPS frequency was obtained in eight patients. MSM therapy was continued chronically in these eight patients, and five continued to have a 50% or greater reduction in CPS frequency after 3 to 34 months of follow-up. Drowsiness, gastrointestinal disturbance, hiccups, irritability, and headache were the common side effects of MSM. No serious toxicity occurred. N-desmethylmethsuximide was the principal substance detected in plasma and had the following pharmacokinetic values: accumulation half-life, 49.7 hours; time to steady state, 10.4 days; elimination half-life, 72.2 hours; therapeutic range of plasma concentration, 10 to 30 mg per liter. Plasma concentrations of phenytoin and phenobarbital derived from primidone rose significantly (p less than 0.05) after addition of MSM.

Interaction between valproic acid and carbamazepine: an in vitro study of protein binding.

Valproic acid (VPA) is highly bound to plasma protein (92-96%) and is likely to compete with carbamazepine (CBZ), another drug that is bound extensively (75%). CBZ protein binding was evaluated in vitro by ultrafiltration at concentrations within the therapeutic range (6, 8, and 12 micrograms/ml), while also varying VPA concentrations (0, 50, and 100 micrograms/ml). Using ultrafiltration, we found a significant elevation (p less than 0.01) in free and percent-free CBZ for every CBZ concentration tested as the total VPA concentration increased. Maximal effect was evident at 12 micrograms/ml CBZ. The free fraction increased from 23.5% free CBZ controls (2.85% micrograms/ml free) to 29.5% free CBZ (3.56% micrograms/ml free), with 100 micrograms/ml VPA a 25% increase in free CBZ. This in vitro study demonstrates that VPA competes with CBZ for plasma protein binding sites, resulting in a significant increase in free CBZ that may be clinically important.