Hypotensive effects of a new transdermal delivery system for clonidine (M-5041T) in spontaneously and renal hypertensive rats.
1. Antihypertensive effects of a new transdermal delivery system for clonidine (clonidine tape; M-50417) were investigated in spontaneously hypertensive rats (SHR), 2-kidney, 1-clip renal hypertensive rats (RHR) and deoxycorticosterone acetate/salt (DOCA/Salt) hypertensive rats. 2. M-5041T (0.5-4.5 mg/kg) elicited long-lasting hypotensive effects and bradycardia in a dose-dependent manner during 24 h patching in three hypertensive models compared with oral clonidine (100 mu g/kg). 3. The most hypotensive effect of M-5041T was observed in DOCA/salt hypertensive rats. 4. Co-administration of M-5041T with either trichloromethiazide (1 mg/kg, orally) or nifedipine (3 mg/kg, orally) at each dose without hypotensive effects per se induced significant hypotension in SHR. 5. Repeated administrations of M-5041T (1.5 mg/kg per day) for a consecutive 7 days produced significant hypotensive effects at postpatching 6 h, and recovered a postpatching 24 h in SHR. 6. Repetitive M-5041T administrations displayed no tolerance on the hypotensive effects and were devoid of any withdrawal syndrome. 7. These findings suggest that M-5041T may serve as an efficiently useful antihypertensive transdermal delivery system in humans.
Ishii
R
R
Central Research Laboratories, Maruho Co. Ltd, Osaka, Japan.
Naruse
T
T
Tagawa
T
T
Ishida
T
T
Namba
K
K
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use; D003000:Clonidine / Q000008:administration & dosage* / Q000627:therapeutic use*; D003900:Desoxycorticosterone; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride; D014237:Trichlormethiazide / Q000008:administration & dosage / Q000627:therapeutic use
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D009543:Nifedipine; D003000:Clonidine; D014237:Trichlormethiazide