Effect of calcium channel modulators on temperature regulation in ovariectomized rats.
Clinical studies evaluating a calcium channel modulator, gabapentin, for the treatment of vasomotor symptoms have been reported. The present studies evaluated three calcium channel modulators in ovariectomized (OVX) rodent models of temperature regulation. Gabapentin, reported to interact with the alpha(2)delta subunit of voltage-sensitive calcium channels and the L-type voltage-gated calcium channel blockers, verapamil and nifedipine, were examined. These series of experiments demonstrated that orally administered gabapentin, verapamil and nifedipine all acutely and dose-dependently lower tail skin temperature in both models of OVX-induced thermoregulatory dysfunction. These compounds all had a rapid onset of action, however, the efficacy of all three calcium channel modulators is less than that observed following chronic estrogen treatment. Additionally, these compounds were also tested in a telemetric rat model measuring core body temperature to evaluate any temperature effects on internal core temperature. The present data suggests that gabapentin, verapamil and nifedipine all act to globally alter temperature regulation in steroid-dependent models of thermoregulatory function.
Leventhal
Liza
L
Women's Health Research Institute, Wyeth Research RN3164, 500 Arcola Rd, Collegeville, PA 19426, USA.
Cosmi
Scott
S
Deecher
Darlene
D
D000588:Amines / Q000494:pharmacology; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D005260:Female; D000077206:Gabapentin; D012739:Gonadal Steroid Hormones / Q000502:physiology; D009021:Morphine Dependence / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D009641:Norethynodrel / Q000031:analogs & derivatives* / Q000494:pharmacology; D010052:Ovariectomy; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000588:Amines; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D003509:Cyclohexanecarboxylic Acids; D012739:Gonadal Steroid Hormones; C002029:17alpha-ethynylestr-5(10)-ene-3alpha,17beta-diol; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009641:Norethynodrel; D014700:Verapamil; D009543:Nifedipine